Polynucleotides, polypeptides, remedies for cancer and vaccines

ABSTRACT

The present invention provides polynucleotides, polypeptides, remedies for cancer, and vaccines, which are used for diagnosing autoimmune diseases such as graft-versus-host disease, and graft-versus-leukemia, and treating and preventing acute or chronic myeloid leukemia. The polynucleotides includes a base sequence that is identical or substantially identical with a base sequence represented by SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, and SEQ ID NO: 10. The polypeptide includes an amino acid sequence that is identical or substantially identical with an amino acid sequence encoded by the above-mentioned polynucleotide. The remedy for cancer contains the polynucleotides or polypeptides, and strengthens the defense mechanism in a living body to thereby treat cancer. The vaccine contains the polynucleotides or polypeptides, and makes living bodies to acquire the defense mechanism to thereby prevent the onset of cancer.

TECHNICAL FIELD

[0001] The present invention relates to polynucleotides, polypeptides, remedies for cancer, and vaccines used for diagnosis of autoimmune diseases such as graft versus host disease (hereafter referred as “GVHD”) and graft versus leukemia (hereafter referred as “GVL”), and for treatment and prevention of cancers such as acute myelogenous leukemia (hereafter referred as “AML”) and chronic myelogenous leukemia (hereafter referred as “CML”).

BACKGROUND ART

[0002] GVHD, which is a kind of autoimmune disease characterized by graft versus host reaction, is a disease in which lymphatic system immunocytes (especially, T cells) of a transplanted donor immunologically attack tissue cells of a recipient (a host) whose gene organization differs, and the tissues of the recipient receive damages. The GVHD frequently occurs after bone marrow transplantation (BMT) for an AML or a CML patient due to the difference of human leukocyte antigen (HLA) between the donor and the recipient. On the other hand, GVL is a kind of autoimmune disease, and is caused by lymphatic system immunocytes of the donor immunologically attacking leukemia cells in the recipient after bone marrow transplantation for the AML or the CML patient.

[0003] Recently, an approach in which cDNA (complementary DNA) library of a human cell or a human cell line is screened using serum of these autoimmune disease patients and then oncogene and target gene of autoimmune disease are identified, has been noticed, and many genes have ever been identified. A polypeptide, which is a product of these genes, includes an antigen that is at least recognized by helper T cells in a living body of the patient. Therefore, the polypeptide has high possibility of becoming a key that causes cancers such as AML and CML and autoimmune diseases such as GVHD and GVL.

DISCLOSURE OF THE INVENTION

[0004] The objectives of the present invention are to provide polynucleotides, polypeptides, remedies for cancer and vaccines used for diagnosis of autoimmune diseases such as GVHD and GVL and for treatment and prevention of AML or CML.

[0005] To achieve the above objectives, the first aspect of the present invention includes a polynucleotide comprising a base sequence that is identical or substantially identical with a base sequence represented by SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, and SEQ ID NO: 10.

[0006] Another aspect of the present invention includes a recombinant vector containing the above-mentioned polynucleotide.

[0007] The further aspect of the present invention includes a transformant containing the above-mentioned recombinant vector.

[0008] The polynucleotide of the present invention may be used with labeled with radioisotope, enzyme, or fluorochrome.

[0009] The further aspect of the present invention includes a polypeptide comprising an amino acid sequence that is identical or substantially identical with an amino acid sequence encoded by the above-mentioned polynucleotide.

[0010] The further aspect of the present invention includes an antibody against the polypeptide of the present invention.

[0011] The further aspect of the present invention includes a hybridoma producing an antibody of the present invention.

[0012] The further aspect of the present invention includes a diagnostic product for autoimmune diseases containing a polypeptide of the present invention.

[0013] The further aspect of the present invention includes a diagnostic kit of autoimmune diseases, which contains the polypeptide of the present invention, for screening serum of a GVHD or a GVL patient.

[0014] The further aspect of the present invention includes a kit for examining diseases, which contains the antibody of the present invention, for analyzing living tissues of an AML, a CML, a GVHD, or a GVL patient.

[0015] The further aspect of the present invention includes a remedy for cancer, which contains the polynucleotide of the present invention or the polypeptide of the present invention, for treating a cancer by strengthening the defense mechanism of a living body against cancer cells.

[0016] The further aspect of the present invention includes a vaccine, which contains the polynucleotide of the present invention or the polypeptide of the present invention, for preventing a cancer by allowing a living body to acquire the defense mechanism of the living body against cancer cells.

[0017] The further aspect of the present invention includes a DNA chip containing the above-mentioned polynucleotide.

BEST MODE FOR CARRYING OUT THE INVENTION

[0018] The present embodiments will be described below in detail.

[0019] The polynucleotide of the present embodiment includes a base sequence represented by SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO:. 8, SEQ ID NO: 9, and SEQ ID NO: 10. The polynucleotide represented by SEQ ID NO: 1 to SEQ ID NO: 10 is a part of human genome cloned from human leukemia K562 cells.

[0020] The polynucleotide including a base sequence represented by SEQ ID NO: 1 and SEQ ID NO: 2 (hereafter referred as “pn1” and “pn2”) encodes a gene product specifically causing antigen-antibody reaction with an antibody contained in serum of an AML patient who developed GVHD after the bone marrow transplantation and is still in a condition of developing GVHD. The polynucleotide including a base sequence represented by each of SEQ ID NO: 3 to SEQ ID NO: 8 (hereafter referred as “pn3” to “pn8”) encodes a gene product specifically causing antigen-antibody reaction with an antibody contained in serum of a CML patient.

[0021] The polynucleotide including a base sequence represented by SEQ ID NO: 9 (hereafter referred as “pn9”) encodes a continuous base sequence of a genome of K562 cells including a base sequence represented by SEQ ID NO: 1. 1-1788 in the sequence is likely to encode open reading frame (ORF). Here, the pn9 is predicted to be confirmed an initiation codon at a position where it slightly extends to an N-terminal side. The polynucleotide including a base sequence represented by SEQ ID NO: 10 (hereafter referred as “pn10”) encodes a continuous base sequence of a genome of K562 cells including a base sequence represented by SEQ ID NO: 2. 277-6921 in the sequence is likely to encode open reading frame (ORF).

[0022] The polynucleotide of the present embodiment includes a base sequence that is substantially identical with a base sequence represented by SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, and SEQ ID NO: 10.

[0023] “a base sequence that is substantially identical with” is an encoded base sequence similar to a base sequence represented by the SEQ ID NOs. having at least one of slight differences selected from deletion, addition, and substitution of partial bases, and has preferably more than 80% homology, more preferably more than 90% homology, and even more preferably more than 95% homology. Alternatively, it contains preferably more than 50%, more preferably more than 75%, and even more preferably more than 95% of base sequences with preferably more than 80% homology, more preferably more than 90% homology, and even more preferably more than 95% homology with respect to the overall length of a base sequence represented by each of the SEQ ID Nos.

[0024] A polynucleotide of the present embodiment may be a polynucleotide fragment or an oligonucleotide fragment obtained by cutting the above-mentioned polynucleotide using various restriction enzymes such as endonuclease, exonuclease, and the like. The polynucleotide fragment or the oligonucleotide fragment may preferably have a length of more than 20 bases, more preferably more than 50 bases, and even more preferably more than 100 bases, and especially preferably more than 500 bases.

[0025] In addition, the substantially identical base sequence may preferably encode an identical or a substantially identical amino acid sequence. “an amino acid sequence that is substantially identical with” is an encoded amino acid sequence having at least one of slight differences selected from deletion, addition, and substitution of partial amino acids, and has preferably more than 80% homology, more preferably more than 90% homology, even more preferably more than 95% homology, and most preferably more than 98% homology.

[0026] The polynucleotide may be stored and amplified in the condition that it is inserted in the predetermined position of a widely used vector in the form of double strand DNA. As the above-mentioned vectors, for example, plasmid vectors derived from Escherichia coli, yeast, or Bacillus subtilis, bacteriophage vectors such as phage λ, or virus vectors such as a retrovirus, an adenovirus, a vaccinia virus, and a baculovirus may preferably be used.

[0027] When the polynucleotide is amplified, a vector including such polynucleotide is initially constructed. Next, the vector is incorporated into an appropriate host cell to produce a transformant, and the transformant is proliferated to amplify the polynucleotide. The above-mentioned host cell may include, for example, bacteria (genus Escherichia, genus Bacillus), yeasts, insect cells, animal cells, or mammalian cells. The vectors and the polynucleotides may easily and massively be produced using these transformants, and then gene product of the polynucleotide may also easily and massively be produced.

[0028] Alternatively, the polynucleotide may massively be obtained by extracting total RNA or messenger RNA (mRNA) fraction from K562 cells, other human cell line, human culture cells, or human tissues, and directly amplifying the extracted solution using RT-PCR method(Reverse Transcriptase Polymerase Chain Reaction Method). Alternatively, the polynucleotide may be obtained by artificial synthesis using an automated DNA synthesis machine.

[0029] On the other hand, the polynucleotide may be used as an antisense DNA or an antisense RNA that is a complementary sequence with respect to a base sequence that is normally expressed as mRNA. More specifically, when at least part of the base sequence of the polynucleotide has a sequence specific for cancer cells of an AML or a CML patient, the specific sequence or a neighboring sequence of the specific sequence including the specific sequence may be used for diagnosis of AML or CML, and thus may assist subsequent treatment. That is, the above-mentioned sequence may be used for a diagnostic probe for well-known methods such as Southern hybridization method, Northern hybridization method, and PCR (Polymerase Chain Reaction) method, after the cancer cells are obtained from the AML or the CML patient. Tissues obtained from the above-mentioned patient may also be used for analyzing expression site or expression condition of the polynucleotide including the above-mentioned sequence, and localization on the human chromosome using in situ hybridization method. Here, the polynucleotide may normally used with labeled with radioisotope, enzyme, or fluorochrome.

[0030] The antisense DNA and the antisense RNA may be used as a remedy for alleviating symptom of autoimmune diseases such as GVHD, GVL, and the like by suppressing the expression level of mRNA of the polynucleotides recognized as an antigen so that the amount of the resultant gene product decreases. When a polynucleotide is one that encodes a polypeptide relating to crisis of a cancer, it may be used as a remedy for cancer for suppressing proliferation of cancer cells by suppressing the production amount of the gene product of the polynucleotide.

[0031] The antisense DNA or the antisense RNA may preferably be administered into a human body independently or with a form in which it is inserted into a retrovirus vector, an adenovirus vector, or an adeno-associated virus vector.

[0032] The polypeptide of the present embodiment includes an amino acid that is identical or a substantially identical with an amino acid encoded by the above-mentioned polynucleotide. That is, it includes an amino acid that is identical or a substantially identical with an amino acid represented by SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, and SEQ ID NO: 10.

[0033] “an amino acid sequence that is substantially identical with” is an encoded amino acid sequence similar to an amino acid sequence having at least one of slight differences selected from deletion, addition, and substitution of partial amino acids. It is encoded with an amino acid sequence having preferably more than 80% homology, more preferably more than 90% homology, even more preferably more than 95% homology, and most preferably more than 98% homology.

[0034] More specifically, when an amino acid sequence is an encoded one having slight differences through the substitution, the property of the amino acid to be substituted may preferably be similar to that of a substituted amino acid. As an example of such pairs of an amino acid to be substituted and a substituted amino acid, glycine and alanine; valine, leucine, and isoleucine; proline, phenylalanine, and tryptophan; aspartic acid and glutamic acid; asparagine and glutamine; serine, threonine, and tyrosine; or lysine, arginine, and histidine may be included. In these substitutions, tertiary structure of a polypeptide is similar in many cases. Therefore, there is high possibility of being recognized to an identical antibody, and there is high possibility of working in a living body of a patient as an antigen that causes autoimmune disease such as GVHD and GVL.

[0035] The polypeptide of the present embodiment may be a polypeptide fragment or an oligopeptide fragment obtained by cutting the polypeptide using a proteolytic enzyme such as protease, proteinase, endopeptidase, exopeptidase, and the like. These polypeptide fragments or oligopeptide fragments have high possibility of working as an antigen that causes autoimmune diseases in a living body of a patient.

[0036] In general, the polypeptides may easily and massively be obtained by compulsorily expressing the polynucleotide inserted into the transformant. Alternatively, it may be obtained by artificially synthesizing with solid phase synthesis method or liquid phase synthesis method. Alternatively, it may also be obtained by fractioning and purifying protein extraction fraction extracted from K562 cells, other human cell line, human culture cells, or human tissues using affinity chromatography carrier with which an antibody against the polypeptide, which is produced in advance, is combined.

[0037] The antibody may include a monoclonal antibody or a polyclonal antibody. The polyclonal antibody may be preferable for increasing diagnosis sensitivity, while the monoclonal antibody may be preferable for detailed diagnosis or analysis. The polyclonal antibody is generally obtained by multiply immunizing an immune animal such as a goat, a rabbit, cattle, and a horse with the polypeptide together with an adjuvant if necessary, and collecting serum from the immune animal. The monoclonal antibody is generally obtained by multiply immunizing an immune animal such as a mouse, a rat, a goat, and a rabbit with the polypeptide together with an adjuvant if necessary, and collecting B cells from the immune animal, cell-fusing the B cells with myeloma cells to produce hybridoma, and obtaining culture supernatant of a single hybridoma that was cloned.

[0038] These antibodies (primary antibodies) may be used as a diagnostic tool or an analyzing tool for analyzing localization where the polypeptide is expressed in tissues or cells (i.e., immunohistochemical staining) with secondary antibodies that are labeled with radioisotope, enzyme, fluorochrome, or the like. Also, it may be used for identification of an antigen that causes GVHD or GVL, or quantitation of the expression level of the polypeptide. When the polypeptide includes physiological activity such as enzymes and the antibody is a neutralizing antibody for such polypeptide, the antibody may be used, for example, as a remedy for cancer since it inhibits the physiological activity of the polypeptide that works as an antigen.

[0039] The remedy for cancer of the present embodiment contains the above-mentioned polynucleotide or polypeptide, and immunologically treats the cancer by strengthening the defense mechanism of a living body against cancer cells in the living body of a cancer patient. The defense mechanism of the living body includes at least one of immune systems selected from antibody-mediated immunity targeting a gene product from the polynucleotide or the polypeptide, and cell-mediated immunity. The cancer cell exposes on the surface of cells in a form in which it recognizes the target as an immunologically not-self, and the main target of the remedy for cancer includes cancer cells of an AML or a CML patient.

[0040] The vaccine of the present embodiment contains the above-mentioned polynucleotide or polypeptide, and immunologically prevents a cancer by allowing a living body to acquire the defense mechanism of the living body against cancer cells. The defense mechanism of the living body includes an identical immune system with that for the remedy for cancer. The vaccine may be used for acquiring the preliminary defense mechanism of a living body to inhibit the occurrence of cancer cells that are exposed on the surface of a cell in the form in which the vaccine recognizes the target as an immunologically not-self. It may mainly be used for preventing morbidity for AML or CML.

[0041] The remedy for cancer or the vaccine of the present embodiment may be used as a mixed remedy for cancer or a mixed vaccine by appropriately mixing at least one selected from the above-mentioned polynucleotides with at least one selected from the above-mentioned polypeptides. In addition, it is preferable that the mixed remedy for cancer may simultaneously contain a polypeptide as a tumor antigen that is included in cancer cells, which is a target for the treatment, and a polynucleotide that encodes the polypeptide.

[0042] The remedy for cancer or the vaccine may be used, for example, in the dosage form of an injection. The injection may contain at least one selected from the polynucleotide and the polypeptide in an isotonic solution containing physiological saline, grape sugar and an adjuvant (e.g., sorbitol and mannitol). If necessary, the injection may include at least one selected from solubilizing agent, buffer for holding pH of a solution constantly, stabilizer (antioxidant) and preservative for improving the stability, and an analgesic agent for alleviating pain during the injection.

[0043] As the solubilizing agent, for example, alcohols such as ethanol, polyethylene glycol, and propylene glycol; nonionic surfactants; fats and oils such as sesame oil and soybean oil; benzyl benzoate; and benzyl alcohol may preferably be used. Preferably, the stabilizer, the preservative and the analgesic agent listed in Japanese pharmacopoeia may be used. In addition, at least one selected from various vitamins, well-known pharmaceutical formulations used for the cancer treatment such as interferons α to γ, physiologically active substances for activating the immune system such as interleukin 1 (α, β), interleukins 2 to 8 and other cytokines may preferably be contained.

[0044] The operations of the above embodiments will now be described.

[0045] When a patient of autoimmune disease such as GVHD or GVL or a person who is suspicious for the autoimmune disease (hereafter, both referred as “a person to be diagnosed”) is diagnosed using the polypeptide, blood from the person to be diagnosed is initially obtained to fractionate its serum. Next, the diagnosis of the autoimmune disease is carried out through examining the antigen-antibody reaction between antibody contained in the serum and the polypeptide.

[0046] Here, for example, quantitative reactions such as immunoprecipitation reaction, double gel diffusion method, and immunoelectrophoresis; and quanitative reactions such as quantitative precipitation reaction, radioimmunoassay, and enzyme-linked immunosorbent assay may be used as the antigen-antibody reaction. When the polypeptide or the protein including the polypeptide has physiological activity such as enzyme, it is possible to confirm the specific antigen-antibody reaction by examining the reduction of the physiological activity and also to prove that the antigen contained in the serum is a neutralizing antibody. In addition, after confirming the existence of the antibody against the polypeptide in the serum of the person to be diagnosed, the tissue is obtained from the person to be diagnosed and the localization of the antigen may immunohistologically be analyzed using an immunohistochemical staining method.

[0047] On the other hand, when the injection containing the polynucleotide as a remedy for cancer is administered into a living body of the AML or the CML patient, the polynucleotide is incorporated into the cells of the patient, is translated, and a resultant gene product is produced. At least part of the produced gene product is processed within cells in various manners and then is fragmented small. Subsequently, the fragmented product is combined with a class I or a class II HLA protein that exists in the cell membrane surface, and then is recognized by T cells as a tumor antigen.

[0048] When the fragmented gene product is combined with the class I HLA protein, cytotoxic T lymphocytes (CTL) in the cancer patient's body recognize the fragment with the tumor antigen, and kill the cells. In addition, this stimulates the CTL, and the CTL is rapidly cell-divided to proliferate. Subsequently, the increased number of CTL after the proliferation circulates in a living body of the patient, finds cells presenting the similar fragment on the HLA protein, i.e., cancer cells, and then kills these cells.

[0049] When the fragmented gene product is combined with the class II HLA protein, helper T cells existing in the patient's body recognize the fragment with a tumor antigen. The information that the fragment is the tumor antigen stimulates B cells to produce antibodies, and transmits the proliferative stimulus to the CTL. Subsequently, the B cells are rapidly cell-divided to proliferate, and then the antibodies that are more specifically combined with the fragment are massively produced. Then, these antibodies are specifically combined with the fragment or the gene product of the polynucleotide, and then immunological attack against the fragment and the gene product by phagocytes such as macrophages and complements of the patient's body may be promoted. When the gene product has physiological activity, the combination of the antibody neutralizes its physiological activity.

[0050] When the injection containing the polypeptide is administered into a living body of the AML or the CML patient as a remedy for cancer, most of the polypeptides are recognized by helper T cells and B cells as a tumor antigen, and a part of the polypeptides are incorporated into cells (mainly, the phagocytes) of the patient's body, and are presented on the cell surface together with class I or class II HLA protein. As a result, as described above, cancer cells are dead through the attack by the immune system including the CTLs, the B cells, the phagocytes, and complements.

[0051] In addition, when the mixed remedy for cancer is administered into a living body of the AML or the CML patient, cell group of immune system is activated against both the gene product of the polynucleotide and the polypeptide, and then additive effect or synergistic effect is displayed. On the other hand, a part of cell group of the immune system (helper T cells, CTLs, B cells) activated by the administration of the remedy for cancer keeps circulating in the living body of the cancer patient as a memory cell, and prevent survived cancer cells or cancer cells that present a similar fragment from proliferating or developing again.

[0052] When a vaccine containing the polynucleotide (a DNA vaccine) is administered into a living body of a human in the form of an injection, the polynucleotide is incorporated in cells of the human's body, and then is translated. As a result, a gene product of the polynucleotide is expressed. As described above, T cells recognize the resultant gene product as an antigen together with class I or class II HLA protein. Therefore, the process of a series of weak immune system activation is passed to exclude the antigen, and finally memory cells are produced. When the vaccine containing the polypeptide is administered into the living body of the human in the form of an injection, the process of a series of weak immune system activation is also passed, and finally memory cells are produced.

[0053] In addition, when the mixed vaccine is administered into a living body of the AML or the CML patient, cell group of immune system is activated against both the gene product of the polynucleotide and the polypeptide, and then additive effect or synergistic effect is displayed. It is preferable that these vaccines are multiply administered at a predetermined interval. As a result, the specificity of the memory cells with respect to the fragment or the gene product is further increased, and the c of cancer cells presenting the similar fragment is further strongly inhibited.

[0054] The above described embodiments have the following effects.

[0055] The polynucleotide of the present invention includes a base sequence that is identical or substantially identical with a base sequence represented by SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, and SEQ ID NO: 10. It is possible to treat a cancer by administering these polynucleotides to an AML or a CML patient, and then strengthening the defense mechanism of a living body of the patient against the cancer cells. In addition, it is possible to prevent development and proliferation of the cancer cells by administering these polynucleotides to a person other than the patient to have the person acquire defense mechanism of a living body against the cancer cells that causes AML or CML.

[0056] The recombinant vector of the present invention is a recombinant vector containing a polynucleotide of the present invention. The recombinant vector allows the polynucleotide to be preserved easily and stably.

[0057] The transformant of the present invention is a transformant containing the recombinant vector of the present invention. The transformant allows the polynucleotide and the vector to be easily amplified to obtain them.

[0058] The polynucleotide of the present invention may be labeled with radioisotope, enzyme or fluorochrome. It is possible to analyze expression of the polynucleotide in the living tissues with high sensitivity, and to assist diagnosis and treatment.

[0059] The polypeptide of the present invention includes an amino acid sequence that is identical or substantially identical with an amino acid sequence encoded by the above-mentioned polynucleotide. It is possible to treat a cancer by administering these polypeptides to an AML or a CML patient, and then strengthening the defense mechanism of a living body of the patient against the cancer cells. In addition, it is possible to prevent development and proliferation of the cancer cells by administering these polynucleotides to a person other than the patient to have the person acquire defense mechanism of a living body against the cancer cells that causes AML or CML. Further, the diagnosis of GVHD or GVL may easily be carried out by examining whether the antigen-antibody reaction occurs against serum of a person to be diagnosed using these polypeptides.

[0060] The antibody of the present invention is an antibody against the polypeptide of the present invention. The use of the antibody may easily analyze the localization of the polypeptide in the living tissues, and thus may assist diagnosis and treatment.

[0061] The hybridoma of the present invention is a hybridoma producing an antibody of the present invention. Monoclonal antibodies, which are able to analyze the localization of the polypeptides in a living body and to assist diagnosis and treatment, may easily and massively be obtained from the hybridoma.

[0062] The diagnostic product for autoimmune diseases of the present invention contains the polypeptide of the present invention, and examines antigen-antibody reaction against an antibody contained in serum of a person to be diagnosed. The diagnostic product may easily carry out the diagnosis for GVHD or GVL.

[0063] The diagnostic kit of autoimmune diseases of the present invention contains the polypeptide of the present invention, and screens serum of a GVHD or a GVL patient. The diagnostic kit may easily carry out the diagnosis for GVHD or GVL.

[0064] The examining kit of the present invention contains the antibody of the present invention, and may analyze living tissues of an AML, a CML, a GVHD, or a GVL patient. It is possible to easily analyze the localization of the polypeptides in a living body, and may assist diagnosis and treatment by using the examining kit.

[0065] The remedy for cancer of the present invention contains at least one selected from the polynucleotide and the polypeptide, and treat cancer by strengthening the defense mechanism of a living body against cancer cells. Therefore, the administration of the remedy for cancer of the present invention may positively induce GVL condition in the living body of the AML or the CML patient, and thus may effectively treat cancer. In addition, the remedy for cancer may be composed of a mixed remedy containing at least one of the polynucleotides and at least one of the polypeptides. This composition may further strengthen the defense mechanism of the living body.

[0066] The vaccine of the present invention contains at least one selected from the polynucleotides and the polypeptides, and makes a living body to acquire the defense mechanism of the living body against cancer cells to prevent the onset and increasing cancer cells. The vaccine may mainly be administered into a person who does not get AML or CML or a person who is likely to genetically get the AML or the CML to effectively prevent the person from getting the AML or the CML. In addition, the vaccine may be composed of a mixed vaccine containing at least one of the polynucleotides and at least one of the polypeptides. This composition may further increase the preventive effect.

[0067] The DNA chip of the present invention is a DNA chip containing the polynucleotide of the present invention. When the DNA chip is used, a monitoring of gene expression may easily be carried out.

EXAMPLES

[0068] Examples that embody the above embodiments will now be described.

[0069] (Screening of cDNA Library)

[0070] Patient A (a woman of 42 year-old) of the high risk case, who is diagnosed with AML M1 Ph1+, was transplanted bone marrow obtained from her elder sister, who matches HLA, in her primary remission phase. The patient A retained the complete remission for a while. However, one and half years later, the reduction of myodynamia in her whole body with muscular atrophy appeared. For this symptom, the treatment with an immunosuppressant and the like was carried out. However, she finally died of the respiratory insufficiency due to the chronic GVHD.

[0071] Cell lysates of various cell lines were analyzed with Western blotting method using mixed serum in which the serum of patient A when the muscular atrophy appeared was mixed with the serum of CML patients B to D. As a result, it was proven that the mixed serum caused strongly specific antigen-antibody reaction in human leukemia cell K562 cells.

[0072] Next, cDNA library was produced from the K562 cells using a random primer (a hexamer). On about 10⁶ clones contained in this library, a phage λ, which contains the cDNA encoding the polypeptide that combines with the antibody in the mixed serum, was screened using serological analysis of antigens by recombinant cDNA expression cloning method (SEREX method). Ten kinds of clones that finally reacted strong-positively were isolated and identified.

[0073] (Characterization)

[0074] The obtained ten kinds of clones were determined their base sequences. As a result, eight kinds of base sequences represented by SEQ ID NO: 1 to SEQ ID No. 8 (i.e., pn1 to pn8) were determined. Here, remaining two kinds of clones overlap with pn3 and pn7, respectively. Here, the clone that overlapped with pn3 (reacting with the serum of patient B) reacted with the serum of patient C. These results and examining results of origin of the serum (patient) in which the gene product of each clone combined are shown in Table 1. TABLE 1 Homology Search Disease name or Result Symptom Patient pn1 novel AML, GVHD after BMT A pn2 novel AML, GVHD after BMT A pn3 novel CML B, C pn4 novel CML C pn5 novel (kif1a) CML C pn6 LEDGF CML C pn7 Sip1 CML C pn8 HSP70 CML D

[0075] (Cloning of pn9 and pn10)

[0076] An oligo-DNA primer that complementarily combines with both ends of each of pn1 and pn2, respectively, was artificially synthesized. The cDNA library was screened using both primers, while each of pn1 and pn2 was extended to the 5′ end side and the 3′ end side. Finally, a base sequence that is regarded as ORF including pn1 or pn2, respectively, i.e., base sequence of pn9 or pn10, was determined.

[0077] (Homology Search)

[0078] Homology search regarding the base sequences of pn1 to pn10 with respect to base sequences of well known nucleic acids that were already registered on the nucleic acid sequence databases was carried out using BLASTN(GENBANK). Regarding some clones, homology search regarding the amino acid sequences encoded by the base sequences with respect to amino acid sequences of well known polypeptides that were already registered on the amino acid sequence databases was carried out using BLASTP(Swiss Plot). In addition, regarding the amino acid sequences, at least one kind of searches selected from the search of the localization using RESORT and the search of the protein motif using MOTIF was carried out.

[0079] Useful information extracted from these search results was shown at the column of “Homology Search Result” of Table 1. It was predicted that pn3 and pn4 have encoded an amino acid sequence with zinc finger domain, and pn5 has encoded an amino acid sequence homologous with the kinesin. In addition, it was predicted that pn9 and pn10 have encoded a protein localized in the nucleus since these have high hydrophobic sites and a plurality of phosphorylation sites.

[0080] In the column of “Homology Search Result” shown in Table 1, “novel” refers that a base sequence and an amino acid sequence with specifically high homology were not confirmed, and pn5 has slightly high homologous with kinesin-like protein (kifla). In Table 1, “LEDGF” refers human epithelium lentis derived growth factor, “Sip1” refers human splicing factor Sip1, and “HSP70” refers 70kD (Dalton) heat shock protein.

[0081] (Verification of Reactivity for Normal Human Serum)

[0082] For the polypeptide produced by phage λ containing each polynucleotide of pn1 to pn10, antigen-antibody reaction was carried out using mixed serum that was obtained by mixing serum obtained from a plurality of healthy persons. The antigen-antibody reaction was not confirmed for each of clones.

[0083] At least one kind of polynucleotides selected from pn1 to pn10 may be used for producing a DNA chip. By using the DNA chip, a monitoring of gene expression for the polynucleotide of each of pn1 to pn10 may easily be carried out.

[0084] The polypeptide of the present invention may be used for a method of diagnosing autoimmune diseases characterized by using the polypeptide for screening serum of a GVHD or a GVL patient. By using the polypeptide, the diagnosis for GVHD or GVL may easily be carried out.

[0085] The antibody of the present invention may be used for a method of examining diseases characterized by analyzing tissues in a living body of an AML, a CML, a GVHD, or a GVL patient. The use of the antibody may easily analyze the localization of the polypeptide in a living body, and thus may assist diagnosis and treatment.

1 10 1 120 DNA Homo sapiens CDS (1)...(120) 1 cag aca aaa tcc tgt cag tcc cag ccc tcc caa act aaa cct tct cca 48 Gln Thr Lys Ser Cys Gln Ser Gln Pro Ser Gln Thr Lys Pro Ser Pro 1 5 10 15 tgc aaa tct act cag cct aag cca agc cag ccc tgg cct ccc cag tct 96 Cys Lys Ser Thr Gln Pro Lys Pro Ser Gln Pro Trp Pro Pro Gln Ser 20 25 30 aag cct tct cag ccc aga ccc cct 120 Lys Pro Ser Gln Pro Arg Pro Pro 35 40 2 3984 DNA Homo sapiens CDS (1)...(3984) 2 agt tta tca gaa gaa cat cag ccc ttt tct gga aaa act gca tat ctg 48 Ser Leu Ser Glu Glu His Gln Pro Phe Ser Gly Lys Thr Ala Tyr Leu 1 5 10 15 ttt tcc cca gac cac tca gat gag aaa cta ata gaa aaa gaa aat caa 96 Phe Ser Pro Asp His Ser Asp Glu Lys Leu Ile Glu Lys Glu Asn Gln 20 25 30 att gat aca gca ttt tta tct agc act agt aaa tat gaa aag ctt gaa 144 Ile Asp Thr Ala Phe Leu Ser Ser Thr Ser Lys Tyr Glu Lys Leu Glu 35 40 45 aaa cat tca gca aat cat aat gtt aaa gat gca act aaa gaa aac agt 192 Lys His Ser Ala Asn His Asn Val Lys Asp Ala Thr Lys Glu Asn Ser 50 55 60 tgt gac gct aat gaa gta ata aat gaa agt aat tct gta tct tta agt 240 Cys Asp Ala Asn Glu Val Ile Asn Glu Ser Asn Ser Val Ser Leu Ser 65 70 75 80 tgc ata aaa gaa aac ata aat tct agt aca ggc aac gat tgt gat gca 288 Cys Ile Lys Glu Asn Ile Asn Ser Ser Thr Gly Asn Asp Cys Asp Ala 85 90 95 act tgc ata ggt cac aca aag gcg aaa act gac gta ctt ata tca gtc 336 Thr Cys Ile Gly His Thr Lys Ala Lys Thr Asp Val Leu Ile Ser Val 100 105 110 tta gat tca aat gtg aag cac ttt tta aat gat ctc tac caa caa ggt 384 Leu Asp Ser Asn Val Lys His Phe Leu Asn Asp Leu Tyr Gln Gln Gly 115 120 125 aac ctt att tta tct gat tgt aaa aga aac ctg gaa gta aag tgg aca 432 Asn Leu Ile Leu Ser Asp Cys Lys Arg Asn Leu Glu Val Lys Trp Thr 130 135 140 gat cct att gag aga ccc ata caa aac att att aca gga aac ttc ctt 480 Asp Pro Ile Glu Arg Pro Ile Gln Asn Ile Ile Thr Gly Asn Phe Leu 145 150 155 160 atg ggc cca tta aac cta act ttg ata gca agt aaa aag tac agt att 528 Met Gly Pro Leu Asn Leu Thr Leu Ile Ala Ser Lys Lys Tyr Ser Ile 165 170 175 cct cag tta tca gcc gct gca gtg aca gat agt gag gga gaa tct tca 576 Pro Gln Leu Ser Ala Ala Ala Val Thr Asp Ser Glu Gly Glu Ser Ser 180 185 190 aaa tct tac ttg gat aag cag aga att ctt act gta gat tct ttt gca 624 Lys Ser Tyr Leu Asp Lys Gln Arg Ile Leu Thr Val Asp Ser Phe Ala 195 200 205 gca tcc agt act gta cca cac tgt gag cag agc tgt aga gaa aaa gag 672 Ala Ser Ser Thr Val Pro His Cys Glu Gln Ser Cys Arg Glu Lys Glu 210 215 220 ctt cta aag aca gaa cag tgc tct tca ggt aat tgc ctc cat aca gat 720 Leu Leu Lys Thr Glu Gln Cys Ser Ser Gly Asn Cys Leu His Thr Asp 225 230 235 240 ggg aat gaa aca aat gtc act gag aat tat gag ttg gat gta gca tca 768 Gly Asn Glu Thr Asn Val Thr Glu Asn Tyr Glu Leu Asp Val Ala Ser 245 250 255 gga act gaa gaa gat aaa agt tat ggg gaa aat ata gtg gaa tta tct 816 Gly Thr Glu Glu Asp Lys Ser Tyr Gly Glu Asn Ile Val Glu Leu Ser 260 265 270 tcc agt gat agt tct ctg ctt tta aaa gat aat gta aaa ggc tcc tct 864 Ser Ser Asp Ser Ser Leu Leu Leu Lys Asp Asn Val Lys Gly Ser Ser 275 280 285 tca gaa aca tgt att gtg aag aaa gac act gag gac aga ata acg tgg 912 Ser Glu Thr Cys Ile Val Lys Lys Asp Thr Glu Asp Arg Ile Thr Trp 290 295 300 aaa gtt aaa caa gcg gaa aaa gca aaa gat tct gtt tac aaa aga agc 960 Lys Val Lys Gln Ala Glu Lys Ala Lys Asp Ser Val Tyr Lys Arg Ser 305 310 315 320 atg act gaa gga tca act gtt aat act gag tac aaa aat caa aag aat 1008 Met Thr Glu Gly Ser Thr Val Asn Thr Glu Tyr Lys Asn Gln Lys Asn 325 330 335 cag atc tca gaa gaa tcc tgc tta aat gag aaa att att aca act aac 1056 Gln Ile Ser Glu Glu Ser Cys Leu Asn Glu Lys Ile Ile Thr Thr Asn 340 345 350 ttg att gat tcc cat ctg agc act aaa aat act acc act gag tca gtc 1104 Leu Ile Asp Ser His Leu Ser Thr Lys Asn Thr Thr Thr Glu Ser Val 355 360 365 cct ttg aag aac aca gtt tct aat ccg ctt aac aaa aga gag aag aac 1152 Pro Leu Lys Asn Thr Val Ser Asn Pro Leu Asn Lys Arg Glu Lys Asn 370 375 380 ccc caa att aaa gtt agt aaa gac tcg cag tct gac ttg aca tta cat 1200 Pro Gln Ile Lys Val Ser Lys Asp Ser Gln Ser Asp Leu Thr Leu His 385 390 395 400 tca gaa ata gcc tat att tcc aaa cca gga att cta gga gtt aat cat 1248 Ser Glu Ile Ala Tyr Ile Ser Lys Pro Gly Ile Leu Gly Val Asn His 405 410 415 acg cct att tta cct gcc cac tct gaa acc tgt aaa gtc cct act ctt 1296 Thr Pro Ile Leu Pro Ala His Ser Glu Thr Cys Lys Val Pro Thr Leu 420 425 430 ctg aag aaa cct gcg tca tac gtg agt gat ttt aaa gaa aaa cat tgc 1344 Leu Lys Lys Pro Ala Ser Tyr Val Ser Asp Phe Lys Glu Lys His Cys 435 440 445 tca gct aat cat acg gcc ctt ata gct aat cta tct caa att ttg cag 1392 Ser Ala Asn His Thr Ala Leu Ile Ala Asn Leu Ser Gln Ile Leu Gln 450 455 460 agg gca gat gaa gca tca tct ttg cag att cta cag gaa gaa act aag 1440 Arg Ala Asp Glu Ala Ser Ser Leu Gln Ile Leu Gln Glu Glu Thr Lys 465 470 475 480 gtt tgt cta aat att ctc cct tta ttt gtg gaa gct ttt gaa aga aag 1488 Val Cys Leu Asn Ile Leu Pro Leu Phe Val Glu Ala Phe Glu Arg Lys 485 490 495 caa gaa tgt tca gtt gaa caa atc ctg att tca aga gaa ctg ttg gta 1536 Gln Glu Cys Ser Val Glu Gln Ile Leu Ile Ser Arg Glu Leu Leu Val 500 505 510 gac caa aac ctg tgg aat aat tgc aaa cac aca tta aaa cca tgt gct 1584 Asp Gln Asn Leu Trp Asn Asn Cys Lys His Thr Leu Lys Pro Cys Ala 515 520 525 gtt gac act ttg gta gaa ctt caa atg atg atg gaa aca att caa ttc 1632 Val Asp Thr Leu Val Glu Leu Gln Met Met Met Glu Thr Ile Gln Phe 530 535 540 att gaa aac aaa aaa agg cac tta gaa ggt gaa cca aca ttg cga agc 1680 Ile Glu Asn Lys Lys Arg His Leu Glu Gly Glu Pro Thr Leu Arg Ser 545 550 555 560 ttg ctt tgg tat gat gaa aca ctg tat gct gag ctt ctt gga aaa cca 1728 Leu Leu Trp Tyr Asp Glu Thr Leu Tyr Ala Glu Leu Leu Gly Lys Pro 565 570 575 cgt gga ttt caa cag cag tct aat ttc tat cct ggt ttc caa gga aga 1776 Arg Gly Phe Gln Gln Gln Ser Asn Phe Tyr Pro Gly Phe Gln Gly Arg 580 585 590 tta aaa tat aat gca ttc tgt gag tta cag act tac cat gat caa tta 1824 Leu Lys Tyr Asn Ala Phe Cys Glu Leu Gln Thr Tyr His Asp Gln Leu 595 600 605 gtt gaa ttg ctt gag gaa aca aaa agg gaa aag aat tca tac tat gta 1872 Val Glu Leu Leu Glu Glu Thr Lys Arg Glu Lys Asn Ser Tyr Tyr Val 610 615 620 ttc tta aag tac aaa cga cag gtt aat gaa tgt gaa gcc ata atg gag 1920 Phe Leu Lys Tyr Lys Arg Gln Val Asn Glu Cys Glu Ala Ile Met Glu 625 630 635 640 cat tgt tcc gat tgc ttt gat ttt tct ctt tct gtt cca ttt acc tgt 1968 His Cys Ser Asp Cys Phe Asp Phe Ser Leu Ser Val Pro Phe Thr Cys 645 650 655 gga gtt aac ttt gga gat agt tta gaa gac ctg gaa atc tta aga aaa 2016 Gly Val Asn Phe Gly Asp Ser Leu Glu Asp Leu Glu Ile Leu Arg Lys 660 665 670 agt act tta aag ttg atc aat gta tgt ggg gac tct cct aaa gtt cat 2064 Ser Thr Leu Lys Leu Ile Asn Val Cys Gly Asp Ser Pro Lys Val His 675 680 685 tcg tat cca gga aaa cag gac cat ctg tgg att atc ata gaa atg atc 2112 Ser Tyr Pro Gly Lys Gln Asp His Leu Trp Ile Ile Ile Glu Met Ile 690 695 700 tcc tca aag gtt aat ttt att aag aac aac gag gca gta cgt gtt aaa 2160 Ser Ser Lys Val Asn Phe Ile Lys Asn Asn Glu Ala Val Arg Val Lys 705 710 715 720 ata tct ctt tat ggt ctg gaa cat atc ttt ttt gat gct gca aaa aat 2208 Ile Ser Leu Tyr Gly Leu Glu His Ile Phe Phe Asp Ala Ala Lys Asn 725 730 735 ctt gtt tgg aaa gag aga aca caa tcc ttc agc aaa aaa tac tca caa 2256 Leu Val Trp Lys Glu Arg Thr Gln Ser Phe Ser Lys Lys Tyr Ser Gln 740 745 750 aag aag gac gaa gaa agg cta ctc aga gtg aat aaa tgt gcc ttt tct 2304 Lys Lys Asp Glu Glu Arg Leu Leu Arg Val Asn Lys Cys Ala Phe Ser 755 760 765 aag ttg cag aag ata tat gat act ttg tct aaa gat tta aac aat gaa 2352 Lys Leu Gln Lys Ile Tyr Asp Thr Leu Ser Lys Asp Leu Asn Asn Glu 770 775 780 cca att tcc cct att ggg ctt gag gag gat act ata att gct tcc aga 2400 Pro Ile Ser Pro Ile Gly Leu Glu Glu Asp Thr Ile Ile Ala Ser Arg 785 790 795 800 aag tca gat cat cca ata acg aag cac att agc ata gaa aat tct aaa 2448 Lys Ser Asp His Pro Ile Thr Lys His Ile Ser Ile Glu Asn Ser Lys 805 810 815 ttt aac agt aat ttg ctt gca cac cca gat att tgt tgt att agt gag 2496 Phe Asn Ser Asn Leu Leu Ala His Pro Asp Ile Cys Cys Ile Ser Glu 820 825 830 ata ttg gat cag gct gaa ttt gca gac ctt aaa aaa tta cag gat ctc 2544 Ile Leu Asp Gln Ala Glu Phe Ala Asp Leu Lys Lys Leu Gln Asp Leu 835 840 845 acc ttg aga tgt aca gat cac tta gaa att tta aaa aaa tac ttt cag 2592 Thr Leu Arg Cys Thr Asp His Leu Glu Ile Leu Lys Lys Tyr Phe Gln 850 855 860 atg cta caa gat aat aac atg gat aat att ttt atc aca gaa gaa aat 2640 Met Leu Gln Asp Asn Asn Met Asp Asn Ile Phe Ile Thr Glu Glu Asn 865 870 875 880 gtt tta gac gtg gtg ata aac cac agc cat gag gct atc att tta aag 2688 Val Leu Asp Val Val Ile Asn His Ser His Glu Ala Ile Ile Leu Lys 885 890 895 cct gaa gct att gaa atg tat att gaa atc gtc atg gtc tca gaa aca 2736 Pro Glu Ala Ile Glu Met Tyr Ile Glu Ile Val Met Val Ser Glu Thr 900 905 910 att cac ttt ctt aaa aac tca ata gca aag aaa cta gac aaa cag agg 2784 Ile His Phe Leu Lys Asn Ser Ile Ala Lys Lys Leu Asp Lys Gln Arg 915 920 925 ttt cga ggt atg ctt tgg ttt gat ttg tca ctt ctt cct gag ctg gtt 2832 Phe Arg Gly Met Leu Trp Phe Asp Leu Ser Leu Leu Pro Glu Leu Val 930 935 940 cag tgc caa gaa aaa atg gct tct ttt tca ttt ctt aaa gat aac tca 2880 Gln Cys Gln Glu Lys Met Ala Ser Phe Ser Phe Leu Lys Asp Asn Ser 945 950 955 960 aca gat gtt tgc ctt tgg aaa gtg ata gag act gct gtt tcc gaa ctt 2928 Thr Asp Val Cys Leu Trp Lys Val Ile Glu Thr Ala Val Ser Glu Leu 965 970 975 aag aaa gat ctg gat att atc tgg caa aat ata atg aaa gct gtt aaa 2976 Lys Lys Asp Leu Asp Ile Ile Trp Gln Asn Ile Met Lys Ala Val Lys 980 985 990 ttt gct cat atg cta ttc att tgc ttc ttc aag gag aac ttc aag gaa 3024 Phe Ala His Met Leu Phe Ile Cys Phe Phe Lys Glu Asn Phe Lys Glu 995 1000 1005 cct ttc aga aat aaa aaa gct tct gaa gaa gtc caa gta tta att cca 3072 Pro Phe Arg Asn Lys Lys Ala Ser Glu Glu Val Gln Val Leu Ile Pro 1010 1015 1020 cat ata ttg acc ttt gtg cca tat ata gca tcc ata aat tat gga agc 3120 His Ile Leu Thr Phe Val Pro Tyr Ile Ala Ser Ile Asn Tyr Gly Ser 1025 1030 1035 1040 act gtg aca gag tta gaa tac aac tac aat caa ttt tct aca ctg ctg 3168 Thr Val Thr Glu Leu Glu Tyr Asn Tyr Asn Gln Phe Ser Thr Leu Leu 1045 1050 1055 aag aat gta atg tct gcc cct agg aaa gat tta gga aaa atg gcc cac 3216 Lys Asn Val Met Ser Ala Pro Arg Lys Asp Leu Gly Lys Met Ala His 1060 1065 1070 att agg aaa gtc atg aaa acg att gaa cat atg aag atg ata tgt act 3264 Ile Arg Lys Val Met Lys Thr Ile Glu His Met Lys Met Ile Cys Thr 1075 1080 1085 aaa aat gct gaa cta acc att tcc ttt ttc cta tgc caa atg ctg tat 3312 Lys Asn Ala Glu Leu Thr Ile Ser Phe Phe Leu Cys Gln Met Leu Tyr 1090 1095 1100 aac aga agg aag att tta cag ctg aag aga aaa gaa aaa atg aat att 3360 Asn Arg Arg Lys Ile Leu Gln Leu Lys Arg Lys Glu Lys Met Asn Ile 1105 1110 1115 1120 cat att gta aaa cct ggg gaa aat aac aat aaa ttt agt att tct acg 3408 His Ile Val Lys Pro Gly Glu Asn Asn Asn Lys Phe Ser Ile Ser Thr 1125 1130 1135 atg ttg ccc cca gta tca gag tgc ata aac aaa aac atc tca aat tcc 3456 Met Leu Pro Pro Val Ser Glu Cys Ile Asn Lys Asn Ile Ser Asn Ser 1140 1145 1150 tct aaa aaa cga ccg agc act gta gac aaa tgt gaa gac tct cag gaa 3504 Ser Lys Lys Arg Pro Ser Thr Val Asp Lys Cys Glu Asp Ser Gln Glu 1155 1160 1165 cag cag caa gat act act gtt tcc agt tgt aaa aag cta aag gta gac 3552 Gln Gln Gln Asp Thr Thr Val Ser Ser Cys Lys Lys Leu Lys Val Asp 1170 1175 1180 atg aaa gat gtc aca aaa atc aac aga gaa aag gca aca ttc aag cat 3600 Met Lys Asp Val Thr Lys Ile Asn Arg Glu Lys Ala Thr Phe Lys His 1185 1190 1195 1200 cca agg act aca gga tct cat ccc aaa agc gaa aac aaa ata gta cca 3648 Pro Arg Thr Thr Gly Ser His Pro Lys Ser Glu Asn Lys Ile Val Pro 1205 1210 1215 agt tca tgt gac agt ctg aaa aga aat cat tta acg cca aaa aag gtt 3696 Ser Ser Cys Asp Ser Leu Lys Arg Asn His Leu Thr Pro Lys Lys Val 1220 1225 1230 gaa atg caa aga tca cta cct ggc tca ctt tta ccc tta gag aac cca 3744 Glu Met Gln Arg Ser Leu Pro Gly Ser Leu Leu Pro Leu Glu Asn Pro 1235 1240 1245 aaa gac act tgc gca tca aag tcg gaa agc aaa ata gac tta act gtt 3792 Lys Asp Thr Cys Ala Ser Lys Ser Glu Ser Lys Ile Asp Leu Thr Val 1250 1255 1260 tca tct gat cac ttc agt gga caa cag gaa aat tta aat agc atg aag 3840 Ser Ser Asp His Phe Ser Gly Gln Gln Glu Asn Leu Asn Ser Met Lys 1265 1270 1275 1280 aaa aga aat gtg aac ttc agt gct gct gaa aca aaa agt gat aag aaa 3888 Lys Arg Asn Val Asn Phe Ser Ala Ala Glu Thr Lys Ser Asp Lys Lys 1285 1290 1295 gat tgt gct gct ttt gca att tgt gac caa aaa agt gta cat ggc aca 3936 Asp Cys Ala Ala Phe Ala Ile Cys Asp Gln Lys Ser Val His Gly Thr 1300 1305 1310 ttt tca cca gac cat ggg aca ctt ttg cag aaa ttt ctt aaa aat tcc 3984 Phe Ser Pro Asp His Gly Thr Leu Leu Gln Lys Phe Leu Lys Asn Ser 1315 1320 1325 3 409 DNA Homo sapiens CDS (1)...(351) 3 agc ttt tgc agg gcc aac cag gct gcc cgc cac gtg tgc ctc aac cag 48 Ser Phe Cys Arg Ala Asn Gln Ala Ala Arg His Val Cys Leu Asn Gln 1 5 10 15 agc atc gac act tac acc atg gtg gac aaa cag act ctg gaa ctc tgc 96 Ser Ile Asp Thr Tyr Thr Met Val Asp Lys Gln Thr Leu Glu Leu Cys 20 25 30 aca ttt gaa gaa ggg agt cag atg gac aac atg ctg gtg caa aca aac 144 Thr Phe Glu Glu Gly Ser Gln Met Asp Asn Met Leu Val Gln Thr Asn 35 40 45 aaa ccc tac aaa tgc aac ttg tgt gac aaa aca ttc tcc act ccc aat 192 Lys Pro Tyr Lys Cys Asn Leu Cys Asp Lys Thr Phe Ser Thr Pro Asn 50 55 60 gag gtt gtt aaa cat tca tgc caa aac cag aac tcg gat gtt ttt gcc 240 Glu Val Val Lys His Ser Cys Gln Asn Gln Asn Ser Asp Val Phe Ala 65 70 75 80 cta gac gaa ggg cga tcc att ctc ctg ggc agt ggg gac tcg gaa gta 288 Leu Asp Glu Gly Arg Ser Ile Leu Leu Gly Ser Gly Asp Ser Glu Val 85 90 95 acg gag cct gac cac cca gtg tta gct tcc atc aaa aag gaa caa gaa 336 Thr Glu Pro Asp His Pro Val Leu Ala Ser Ile Lys Lys Glu Gln Glu 100 105 110 acc gtc tta cta gac tgaatgtcac ttatcttttt aaaaaactct catttttaca 391 Thr Val Leu Leu Asp 115 aagactatct tccctccc 409 4 607 DNA Homo sapiens CDS (1)...(606) 4 gga agg gaa att cgt gaa ttg aaa gaa ctt cag gat gaa gga aga agt 48 Gly Arg Glu Ile Arg Glu Leu Lys Glu Leu Gln Asp Glu Gly Arg Ser 1 5 10 15 gca cga ttc agt gtc ctc agt gtg tgt ttg gta cca att gcc cta aaa 96 Ala Arg Phe Ser Val Leu Ser Val Cys Leu Val Pro Ile Ala Leu Lys 20 25 30 cat ttg tgc aac atg cta aaa ccc atg aaa aag ata aaa ggt act act 144 His Leu Cys Asn Met Leu Lys Pro Met Lys Lys Ile Lys Gly Thr Thr 35 40 45 gct gtg aag agt gaa ctt cag gca gtg aca gaa aat gaa ttg gaa tgc 192 Ala Val Lys Ser Glu Leu Gln Ala Val Thr Glu Asn Glu Leu Glu Cys 50 55 60 cat cga ggc att gca cat ggg gca gtg gta aaa tgc cct atg gtc act 240 His Arg Gly Ile Ala His Gly Ala Val Val Lys Cys Pro Met Val Thr 65 70 75 80 tct gat att gcc cag aga aaa aca caa aaa aag act ttc atg aaa gac 288 Ser Asp Ile Ala Gln Arg Lys Thr Gln Lys Lys Thr Phe Met Lys Asp 85 90 95 tct gta gta gga tca tcc aaa aaa tca gct acc tac ata tgt aag atg 336 Ser Val Val Gly Ser Ser Lys Lys Ser Ala Thr Tyr Ile Cys Lys Met 100 105 110 tgt cct ttt act act tca gcc aaa agt gtt tta aaa aag cac acg gag 384 Cys Pro Phe Thr Thr Ser Ala Lys Ser Val Leu Lys Lys His Thr Glu 115 120 125 tac ttg cat tca tca tca tgt gtt gat tca ttt ggt agt cct ctt gga 432 Tyr Leu His Ser Ser Ser Cys Val Asp Ser Phe Gly Ser Pro Leu Gly 130 135 140 ctt gat aaa aga aaa aat gac atc ctt gaa gaa cct gta gat agt gat 480 Leu Asp Lys Arg Lys Asn Asp Ile Leu Glu Glu Pro Val Asp Ser Asp 145 150 155 160 agc act aaa aca tta act aaa caa cag tca acc aca ttt cca aag aac 528 Ser Thr Lys Thr Leu Thr Lys Gln Gln Ser Thr Thr Phe Pro Lys Asn 165 170 175 tct gct tta aaa caa gat gtg aag cga aca ttt gga tca acc tca caa 576 Ser Ala Leu Lys Gln Asp Val Lys Arg Thr Phe Gly Ser Thr Ser Gln 180 185 190 tca agt agt ttt tca aaa att cat aag cgg c 607 Ser Ser Ser Phe Ser Lys Ile His Lys Arg 195 200 5 398 DNA Homo sapiens CDS (34)...(396) 5 tgggaccccg cgcgggctgg ttcgggatga gcg atg gca tcg gtc aag gtg gcc 54 Met Ala Ser Val Lys Val Ala 1 5 gtg agg gtc cgg ccc atg aat cgc agg gaa aag gac ttg gag gcc aag 102 Val Arg Val Arg Pro Met Asn Arg Arg Glu Lys Asp Leu Glu Ala Lys 10 15 20 ttc att att cag atg gag aaa agc aaa acg aca atc aca aac tta aag 150 Phe Ile Ile Gln Met Glu Lys Ser Lys Thr Thr Ile Thr Asn Leu Lys 25 30 35 ata cca gaa gga ggc act ggg gac tca gga aga gaa cgg acc aag acc 198 Ile Pro Glu Gly Gly Thr Gly Asp Ser Gly Arg Glu Arg Thr Lys Thr 40 45 50 55 ttc acc tat gac ttt tct ttt tat tct gct gat aca aaa agc cca gat 246 Phe Thr Tyr Asp Phe Ser Phe Tyr Ser Ala Asp Thr Lys Ser Pro Asp 60 65 70 tac gtt tca caa gaa atg gtt ttc aaa acc ctc ggc aca gat gtc gtg 294 Tyr Val Ser Gln Glu Met Val Phe Lys Thr Leu Gly Thr Asp Val Val 75 80 85 aag tct gca ttt gaa ggt tat aat gct tgt gtc ttt gca tat ggg caa 342 Lys Ser Ala Phe Glu Gly Tyr Asn Ala Cys Val Phe Ala Tyr Gly Gln 90 95 100 act gga tct gga aag tca tac act atg atg gga aat tct gga gat tct 390 Thr Gly Ser Gly Lys Ser Tyr Thr Met Met Gly Asn Ser Gly Asp Ser 105 110 115 ggc tta at 398 Gly Leu 120 6 2567 DNA Homo sapiens CDS (1)...(1122) 6 gta gaa act gag gag gca gga gta gtg aca aca gca aca gca tct gtt 48 Val Glu Thr Glu Glu Ala Gly Val Val Thr Thr Ala Thr Ala Ser Val 1 5 10 15 aat cta aaa gtg agt cct aaa aga gga cga cct gca gct aca gaa gtc 96 Asn Leu Lys Val Ser Pro Lys Arg Gly Arg Pro Ala Ala Thr Glu Val 20 25 30 aag att cca aaa cca aga ggc aga ccc aaa atg gta aaa cag ccc tgt 144 Lys Ile Pro Lys Pro Arg Gly Arg Pro Lys Met Val Lys Gln Pro Cys 35 40 45 cct tca gag agt gac atc att act gaa gag gac aaa agt aag aaa aag 192 Pro Ser Glu Ser Asp Ile Ile Thr Glu Glu Asp Lys Ser Lys Lys Lys 50 55 60 ggg caa gag gaa aaa caa cct aaa aag cag cct aag aag gat gaa gag 240 Gly Gln Glu Glu Lys Gln Pro Lys Lys Gln Pro Lys Lys Asp Glu Glu 65 70 75 80 ggc cag aag gaa gaa gat aag cca aga aaa gag ccg gat aaa aaa gag 288 Gly Gln Lys Glu Glu Asp Lys Pro Arg Lys Glu Pro Asp Lys Lys Glu 85 90 95 ggg aag aaa gaa gtt gaa tca aaa agg aaa aat tta gct aaa aca ggg 336 Gly Lys Lys Glu Val Glu Ser Lys Arg Lys Asn Leu Ala Lys Thr Gly 100 105 110 gtt act tca acc tcc gat tct gaa gaa gaa gga gat gat caa gaa ggt 384 Val Thr Ser Thr Ser Asp Ser Glu Glu Glu Gly Asp Asp Gln Glu Gly 115 120 125 gaa aag aag aga aaa ggt ggg agg aac ttt cag act gct cac aga agg 432 Glu Lys Lys Arg Lys Gly Gly Arg Asn Phe Gln Thr Ala His Arg Arg 130 135 140 aat atg ctg aaa ggc caa cat gag aaa gaa gca gca gat cga aaa cgc 480 Asn Met Leu Lys Gly Gln His Glu Lys Glu Ala Ala Asp Arg Lys Arg 145 150 155 160 aag caa gag gaa caa atg gaa act gag cag cag aat aaa gat gaa gga 528 Lys Gln Glu Glu Gln Met Glu Thr Glu Gln Gln Asn Lys Asp Glu Gly 165 170 175 aag aag cca gaa gtt aag aaa gtg gag aag aag cga gaa aca tca atg 576 Lys Lys Pro Glu Val Lys Lys Val Glu Lys Lys Arg Glu Thr Ser Met 180 185 190 gat tct cga ctt caa agg ata cat gct gag att aaa aat tca ctc aaa 624 Asp Ser Arg Leu Gln Arg Ile His Ala Glu Ile Lys Asn Ser Leu Lys 195 200 205 att gat aat ctt gat gtg aac aga tgc att gag gcc ttg gat gaa ctt 672 Ile Asp Asn Leu Asp Val Asn Arg Cys Ile Glu Ala Leu Asp Glu Leu 210 215 220 gct tca ctt cag gtc aca atg caa caa gct cag aaa cac aca gag atg 720 Ala Ser Leu Gln Val Thr Met Gln Gln Ala Gln Lys His Thr Glu Met 225 230 235 240 att act aca ctg aaa aaa ata cgg cga ttc aaa gtt agt cag gta atc 768 Ile Thr Thr Leu Lys Lys Ile Arg Arg Phe Lys Val Ser Gln Val Ile 245 250 255 atg gaa aag tct aca atg ttg tat aac aag ttt aag aac atg ttc ttg 816 Met Glu Lys Ser Thr Met Leu Tyr Asn Lys Phe Lys Asn Met Phe Leu 260 265 270 gtt ggt gaa gga gat tcc gtg atc acc caa gtg ctg aat aaa tct ctt 864 Val Gly Glu Gly Asp Ser Val Ile Thr Gln Val Leu Asn Lys Ser Leu 275 280 285 gct gaa caa aga cag cat gag gaa gcg aat aaa acc aaa gat caa ggg 912 Ala Glu Gln Arg Gln His Glu Glu Ala Asn Lys Thr Lys Asp Gln Gly 290 295 300 aag aaa ggg cca aac aaa aag cta gag aag gaa caa aca ggg tca aag 960 Lys Lys Gly Pro Asn Lys Lys Leu Glu Lys Glu Gln Thr Gly Ser Lys 305 310 315 320 act cta aat gga gga tct gat gct caa gat ggt aat cag cca caa cat 1008 Thr Leu Asn Gly Gly Ser Asp Ala Gln Asp Gly Asn Gln Pro Gln His 325 330 335 aac ggg gag agc aat gaa gac agc aaa gac aac cat gaa gcc agc acg 1056 Asn Gly Glu Ser Asn Glu Asp Ser Lys Asp Asn His Glu Ala Ser Thr 340 345 350 aag aaa aag cca tcc agt gaa gag aga gag act gaa ata tct ctg aag 1104 Lys Lys Lys Pro Ser Ser Glu Glu Arg Glu Thr Glu Ile Ser Leu Lys 355 360 365 gat tct aca cta gat aac taggttgaca tacctggaat atagagaaca 1152 Asp Ser Thr Leu Asp Asn 370 cttgagaagt ttgtaatggt tttcatttga aatagactgc tggaagttta aatttttata 1212 agcataggtt tgatgttgaa aacttgtttt gagggagaaa atccctttgt tttaaagtaa 1272 agtaaacatt atcgctaagt gtaacttgtg cagtattaac agctacatta tacagtaaat 1332 gtgggataaa atccatttag aaaatgttaa actgcttttc cagacatggt tgtagcatat 1392 tttcaattag tgtgtgtatg ttaatgtgta attgatagta gaacaaagtt acatttttaa 1452 aactgctact tgtataaacc ttgcctcttt tcccaaatac tgtgggtttt gtgcatagtt 1512 tttacaaacc ttggatttac cagactgtct tttcactgtt tgtgggtttt gtagaagtta 1572 cacattttta tggtagataa aatgttactt ctatacaagt actcactccc tttttatcaa 1632 aagttaattt taatctcaca gtctacattg tgctacatta tccagcttct ttggaacaat 1692 gtgtgctctg tatggttttt tttggtatga caactaatta agcaactgac attgaactga 1752 gaattctaca aactataaaa cattaatttt tgaaggtaat ttagttttgt ggctgggcat 1812 tcagtgaagt cttaggactt ctttgcagac aactgactgg gtatatatag gaatgaatct 1872 ggctttaggg ttaaatcatt taaggtcctt ttataggcag gcactagtaa ctaaaactga 1932 aaactaagta agtttatttt tgaggaatgt tgttaaaaat gtctttagga agtcactaaa 1992 acttaattgg aagaaaaaat catgatgctt atacaataaa tatgaataaa tgttatataa 2052 ggaaactcac ctatttgaaa tcatggctat attgttttta ttttctagat tccaaaaata 2112 caaacactag ttgttccagc attgtacttt gataagtctg tacattgacg tgtatggact 2172 aaatccaggg taaaatcaat gttacaaaat ttaagggtat gttaactaaa ggatagcatt 2232 tctaagatat tttgaatatt agggtcattt ggcacttctc agcaagtagg atacttctca 2292 tgtttttgaa attatatgaa tatggaaaaa aatggcttaa gaccagcgtc tctgtatgac 2352 attgtgtggt tgaccctctg agataactgt tttcatctac agaattgcat ttttgctttt 2412 aaagaggtct tataatggaa ctaggaatca ccgttttgag agaacctgca tatataccag 2472 tcattatctg tttggtcctt atacagtttt aacttactta gatttattct agttaagcca 2532 taagttcaac gtgtaaactt gttttcatta aagaa 2567 7 1173 DNA Homo sapiens CDS (1)...(543) 7 ccc cca cca tcc caa caa gtc aac tac att gct tca caa cca gat gga 48 Pro Pro Pro Ser Gln Gln Val Asn Tyr Ile Ala Ser Gln Pro Asp Gly 1 5 10 15 aag caa ttg cag ggt att cct agt tct tct cat gta agt aat aac atg 96 Lys Gln Leu Gln Gly Ile Pro Ser Ser Ser His Val Ser Asn Asn Met 20 25 30 agt aca cca gtt ttg cct gct ccg aca gca gcc cca gga aat acg gga 144 Ser Thr Pro Val Leu Pro Ala Pro Thr Ala Ala Pro Gly Asn Thr Gly 35 40 45 atg gtt cag gga cca agt tct ggt aat act tcg tca tca agt cac agc 192 Met Val Gln Gly Pro Ser Ser Gly Asn Thr Ser Ser Ser Ser His Ser 50 55 60 aaa gcc tct aat gct gct gta aaa ttg gca gaa agc aaa gta agt gtt 240 Lys Ala Ser Asn Ala Ala Val Lys Leu Ala Glu Ser Lys Val Ser Val 65 70 75 80 gca gtg gaa gcc agc gca gat agc tcg aag aca gac aag aaa ttg caa 288 Ala Val Glu Ala Ser Ala Asp Ser Ser Lys Thr Asp Lys Lys Leu Gln 85 90 95 att caa gaa aaa gca gca caa gag gta aaa ttg gcc atc aag cca ttt 336 Ile Gln Glu Lys Ala Ala Gln Glu Val Lys Leu Ala Ile Lys Pro Phe 100 105 110 tac caa aat aaa gat atc acc aag gaa gaa tat aaa gaa att gta cgg 384 Tyr Gln Asn Lys Asp Ile Thr Lys Glu Glu Tyr Lys Glu Ile Val Arg 115 120 125 aaa gca gta gat aaa gtt tgt cat agt aag agt gga gaa gta aat tct 432 Lys Ala Val Asp Lys Val Cys His Ser Lys Ser Gly Glu Val Asn Ser 130 135 140 act aaa gtg gca aat ctg gtt aaa gcc tat gta gac aaa tac aaa tat 480 Thr Lys Val Ala Asn Leu Val Lys Ala Tyr Val Asp Lys Tyr Lys Tyr 145 150 155 160 tca cgg aag ggg agc caa aag aaa act ctg gaa gaa cct gtg tct act 528 Ser Arg Lys Gly Ser Gln Lys Lys Thr Leu Glu Glu Pro Val Ser Thr 165 170 175 gaa aaa aac ata ggc tgaaatgggg aacgctgtca aggacattat caggatatct 583 Glu Lys Asn Ile Gly 180 gcaaagtgca atttcaacat gtaccattaa ctgaaaatca tacataactg tgattgaaat 643 ttggttttga taaaattatt tttttaacat aggatatgat gttttgttct aaataaatat 703 aggtctgcac tgcaacttct gtatccttcc ttcccctcca ccctccccca caaaattcaa 763 gggaaagtaa agggtttaaa ggaatgtgca tctttactag gactgtgtta tagtgtggat 823 actggaaaat gtatagcttt ttgattaggg caatggagtg cataaattag aaactttcta 883 agtgcactgg ttttcaaaga gatatatata atgcatttat tctgtcaggt taaaatataa 943 agtatgatct ttatgatttt ttccctctaa ttatagaaag ttaaataatg tattaccatg 1003 aaaaatgttt ctaatattaa atagaacata tcagttgcaa agttcctaat gtgtattttt 1063 aaagcacata tctgaataaa ttgcctagat agaaaaaaaa ttatcatcga gtaaaattta 1123 gtgttcaaaa cattgagaca ctcttcacct attgtatgac caaataaagg 1173 8 2131 DNA Homo sapiens CDS (1034)...(2131) 8 tgcggccgca cctgcaggcg cagagtaggt atggaagatc cctcgagatc cattgtgctc 60 taaagccgcc gggggtccgt gtcctgtctc ggttggccgg acccgggccc gagcccgagc 120 agtagccggc gccatgtcgg tggtgggcat agacctgggc ttccagagct gctacgtcgc 180 tgtggcccgc gccggcggca tcgagactat cgctaatgag tatagcgacc gctgcacgcc 240 ggcttgcatt tcttttggtc ctaagaatcg ttcaattgga gcagcagcta aaagccaggt 300 aatttctaat gcaaagaaca cagtccaagg atttaaaaga ttccatggcc gagcattctc 360 tgatccattt gtggaggcag aaaaatctaa ccttgcatat gatattgtgc agtggcctac 420 aggattaaca ggtataaagg tgacatatat ggaggaagag cgaaatttta ccactgagca 480 agtgactgcc atgcttttgt ccaaactgaa ggagacagcc gaaagtgttc ttaagaagcc 540 tgtagttgac tgtgttgttt cggttccttg tttctatact gatgcagaaa gacgatcagt 600 gatggatgca acacagattg ctggtcttaa ttgcttgcga ttaatgaatg aaaccactgc 660 agttgctctt gcatatggaa tctataagca ggatcttcct cgcttagaag agaaaccaag 720 aaatgtagtt tttgtagaca tgggccactc tgcttatcaa gtttctgtat gtgcatttaa 780 tagaggaaaa ctgaaagttc tggccactgc atttgacacg acattgggag gtagaaaatt 840 tgatgaagtg ttagtaaatc acttctgtga agaatttggg aagaaataca agctagacat 900 taagtccaaa atccgtgcat tattacgact ctctcaggag tgtgagaaac tcaagaaatt 960 gatgagtgca aatgcttcag atctcccttt gagcattgaa tgttttatga atgatgttga 1020 tgtatctgga act atg aat aga ggc aaa ttt ctg gag atg tgc aat gat 1069 Met Asn Arg Gly Lys Phe Leu Glu Met Cys Asn Asp 1 5 10 ctc tta gct aga gtg gag cca cca ctt cgt agt gtt ttg gaa caa acc 1117 Leu Leu Ala Arg Val Glu Pro Pro Leu Arg Ser Val Leu Glu Gln Thr 15 20 25 aag tta aag aaa gaa gat att tat gca gtg gag ata gtt ggt ggt gct 1165 Lys Leu Lys Lys Glu Asp Ile Tyr Ala Val Glu Ile Val Gly Gly Ala 30 35 40 aca cga atc cct gcg gta aaa gag aag atc agc aaa ttt ttc ggt aaa 1213 Thr Arg Ile Pro Ala Val Lys Glu Lys Ile Ser Lys Phe Phe Gly Lys 45 50 55 60 gaa ctt agt aca aca tta aat gct gat gaa gct gtc act cga ggc tgt 1261 Glu Leu Ser Thr Thr Leu Asn Ala Asp Glu Ala Val Thr Arg Gly Cys 65 70 75 gca ttg cag tgt gcc atc tta tcg cct gct ttc aaa gtc aga gaa ttt 1309 Ala Leu Gln Cys Ala Ile Leu Ser Pro Ala Phe Lys Val Arg Glu Phe 80 85 90 tct atc act gat gta gta cca tat cca ata tct ctg aga tgg aat tct 1357 Ser Ile Thr Asp Val Val Pro Tyr Pro Ile Ser Leu Arg Trp Asn Ser 95 100 105 cca gct gaa gaa ggg tca agt gac tgt gaa gtc ttt tcc aaa aat cat 1405 Pro Ala Glu Glu Gly Ser Ser Asp Cys Glu Val Phe Ser Lys Asn His 110 115 120 gct gct cct ttc tct aaa gtt ctt aca ttt tat aga aag gaa cct ttc 1453 Ala Ala Pro Phe Ser Lys Val Leu Thr Phe Tyr Arg Lys Glu Pro Phe 125 130 135 140 act ctt gag gcc tac tac agc tct cct cag gat ttg ccc tat cca gat 1501 Thr Leu Glu Ala Tyr Tyr Ser Ser Pro Gln Asp Leu Pro Tyr Pro Asp 145 150 155 cct gct ata gct cag ttt tca gtt cag aaa gtc act cct cag tct gat 1549 Pro Ala Ile Ala Gln Phe Ser Val Gln Lys Val Thr Pro Gln Ser Asp 160 165 170 ggc tcc agt tca aaa gtg aaa gtc aaa gtt cga gta aat gtc cat ggc 1597 Gly Ser Ser Ser Lys Val Lys Val Lys Val Arg Val Asn Val His Gly 175 180 185 att ttc agt gtg tcc agt gca tct tta gtg gag gtt cac aag tct gag 1645 Ile Phe Ser Val Ser Ser Ala Ser Leu Val Glu Val His Lys Ser Glu 190 195 200 gaa aat gag gag cca atg gaa aca gat cag aat gca aag gag gaa gag 1693 Glu Asn Glu Glu Pro Met Glu Thr Asp Gln Asn Ala Lys Glu Glu Glu 205 210 215 220 aag atg caa gtg gac cag gag gaa cca cat gtt gaa gag caa cag cag 1741 Lys Met Gln Val Asp Gln Glu Glu Pro His Val Glu Glu Gln Gln Gln 225 230 235 cag aca cca gca gaa aat aag gca gag tct gaa gaa atg gag acc tct 1789 Gln Thr Pro Ala Glu Asn Lys Ala Glu Ser Glu Glu Met Glu Thr Ser 240 245 250 caa gct gga tcc aag gat aaa aag atg gac caa cca ccc caa tgc caa 1837 Gln Ala Gly Ser Lys Asp Lys Lys Met Asp Gln Pro Pro Gln Cys Gln 255 260 265 gaa ggc aaa agt gaa gac cag tac tgt gga cct gcc aat cga gaa tca 1885 Glu Gly Lys Ser Glu Asp Gln Tyr Cys Gly Pro Ala Asn Arg Glu Ser 270 275 280 gct ata tgg cag ata gac aga gag atg ctc aac ttg tac att gaa aat 1933 Ala Ile Trp Gln Ile Asp Arg Glu Met Leu Asn Leu Tyr Ile Glu Asn 285 290 295 300 gag ggt aag atg atc atg cag gat aaa ctg gag aag gag cgg aat gat 1981 Glu Gly Lys Met Ile Met Gln Asp Lys Leu Glu Lys Glu Arg Asn Asp 305 310 315 gct aag aac gca gtg gag gaa tat gtg tat gaa atg aga gac aag ctt 2029 Ala Lys Asn Ala Val Glu Glu Tyr Val Tyr Glu Met Arg Asp Lys Leu 320 325 330 agt ggt gaa tat gag aag ttt gtg agt gaa gat gat cgt aac agt ttt 2077 Ser Gly Glu Tyr Glu Lys Phe Val Ser Glu Asp Asp Arg Asn Ser Phe 335 340 345 act ttg aaa ctg gaa gat act gaa aat tgg ttg tat gag gat gga gaa 2125 Thr Leu Lys Leu Glu Asp Thr Glu Asn Trp Leu Tyr Glu Asp Gly Glu 350 355 360 gac cag 2131 Asp Gln 365 9 2106 DNA Homo sapiens CDS (1)...(1788) 9 gga tca gaa aag ttt ctg act ctc atg aag atg cca gtc atc tct ttt 48 Gly Ser Glu Lys Phe Leu Thr Leu Met Lys Met Pro Val Ile Ser Phe 1 5 10 15 gtg cgt cta gga tac tgt agc ttc tct aag tcc aga atc ctc aac aca 96 Val Arg Leu Gly Tyr Cys Ser Phe Ser Lys Ser Arg Ile Leu Asn Thr 20 25 30 ctt ctc agc cct gcc cag ttg aaa tta cac aaa atc ttt ctt cat caa 144 Leu Leu Ser Pro Ala Gln Leu Lys Leu His Lys Ile Phe Leu His Gln 35 40 45 gat ttg cct ctt ttg gtg ctt ccc cgg caa atc tct gat ggc ctg gtt 192 Asp Leu Pro Leu Leu Val Leu Pro Arg Gln Ile Ser Asp Gly Leu Val 50 55 60 gag ata aca tgg tgt ttt cct gat agc gat gat aga aag gaa aac ccc 240 Glu Ile Thr Trp Cys Phe Pro Asp Ser Asp Asp Arg Lys Glu Asn Pro 65 70 75 80 ttt ttc caa aag cct gtt gct ctg gct aat ctc cgt gga aat cta gaa 288 Phe Phe Gln Lys Pro Val Ala Leu Ala Asn Leu Arg Gly Asn Leu Glu 85 90 95 agc ttt tgg act cag ttt ggt ttt ttg atg gaa gtt tct tca gct gtg 336 Ser Phe Trp Thr Gln Phe Gly Phe Leu Met Glu Val Ser Ser Ala Val 100 105 110 ttt ttt ttc act gac tgt tta ggt gag aag gaa tgg gac ttg cta atg 384 Phe Phe Phe Thr Asp Cys Leu Gly Glu Lys Glu Trp Asp Leu Leu Met 115 120 125 ttt tta gga gag gct gcc att gaa aga tgc tac ttt gtt ctc agt tcc 432 Phe Leu Gly Glu Ala Ala Ile Glu Arg Cys Tyr Phe Val Leu Ser Ser 130 135 140 caa gcc agg gag agt gaa gag gct caa att ttt cag agg ata ctg aac 480 Gln Ala Arg Glu Ser Glu Glu Ala Gln Ile Phe Gln Arg Ile Leu Asn 145 150 155 160 ttg aag cca gca cag cta ctg ttt tgg gag agg gga gat gct ggg gat 528 Leu Lys Pro Ala Gln Leu Leu Phe Trp Glu Arg Gly Asp Ala Gly Asp 165 170 175 aga agg aag aac atg gag ggc ctt caa gct gcc ctc cag gaa gtg atg 576 Arg Arg Lys Asn Met Glu Gly Leu Gln Ala Ala Leu Gln Glu Val Met 180 185 190 ttc tct tct tgc ctc aga tgt gtg tct gtg gag gat atg gcc gcc ctg 624 Phe Ser Ser Cys Leu Arg Cys Val Ser Val Glu Asp Met Ala Ala Leu 195 200 205 gcc agg gag ctg ggg att cag gta gat gaa gac ttt gaa aac act cag 672 Ala Arg Glu Leu Gly Ile Gln Val Asp Glu Asp Phe Glu Asn Thr Gln 210 215 220 aga att caa gtt tcc tct gga gaa aac atg gct ggg aca gct gaa ggt 720 Arg Ile Gln Val Ser Ser Gly Glu Asn Met Ala Gly Thr Ala Glu Gly 225 230 235 240 gag ggt cag caa aga cac agt cag cta aaa agc tca tct aaa agc cag 768 Glu Gly Gln Gln Arg His Ser Gln Leu Lys Ser Ser Ser Lys Ser Gln 245 250 255 gct cta atg cca att caa gag cct ggg act caa tgt gag ctc agc cag 816 Ala Leu Met Pro Ile Gln Glu Pro Gly Thr Gln Cys Glu Leu Ser Gln 260 265 270 aat ctt cag aat ctc tat ggt acc cca gta ttc agg cct gtt cta gag 864 Asn Leu Gln Asn Leu Tyr Gly Thr Pro Val Phe Arg Pro Val Leu Glu 275 280 285 aac tcc tgg ctc ttt cca acc aga att gga ggt aac ttt aac cat gtt 912 Asn Ser Trp Leu Phe Pro Thr Arg Ile Gly Gly Asn Phe Asn His Val 290 295 300 tcc ttg aaa gcc tcc tgg gtt atg ggc cgc ccc ttt ggg tca gag cag 960 Ser Leu Lys Ala Ser Trp Val Met Gly Arg Pro Phe Gly Ser Glu Gln 305 310 315 320 agg cct aag tgg ttc cat cct ttg cct ttt cag aat gca ggg gcc cag 1008 Arg Pro Lys Trp Phe His Pro Leu Pro Phe Gln Asn Ala Gly Ala Gln 325 330 335 ggc cga ggt aaa agt ttt ggt att caa tcc ttc cat ccc cag ata ttt 1056 Gly Arg Gly Lys Ser Phe Gly Ile Gln Ser Phe His Pro Gln Ile Phe 340 345 350 tat tca ggt gaa aga ttc atg aaa ttt tcc aga gtt gct cgg gga tgt 1104 Tyr Ser Gly Glu Arg Phe Met Lys Phe Ser Arg Val Ala Arg Gly Cys 355 360 365 cac tcg aat gga aca ttt ggg aga ctg cca aga ccc att tgt cag cat 1152 His Ser Asn Gly Thr Phe Gly Arg Leu Pro Arg Pro Ile Cys Gln His 370 375 380 gta cag gcc tgc cct gag aga cca caa atg atg gga act ctt gaa agg 1200 Val Gln Ala Cys Pro Glu Arg Pro Gln Met Met Gly Thr Leu Glu Arg 385 390 395 400 tct agg gca gta gcc tcc aag ata ggt cac tcc tat tcc ctg gat tca 1248 Ser Arg Ala Val Ala Ser Lys Ile Gly His Ser Tyr Ser Leu Asp Ser 405 410 415 cag cca gca aga gca gta ggg aag cca tgg cct cag caa gct tgc acc 1296 Gln Pro Ala Arg Ala Val Gly Lys Pro Trp Pro Gln Gln Ala Cys Thr 420 425 430 agg gta aca gag tta act gaa gca act gga aaa ctg ata aga aca tcc 1344 Arg Val Thr Glu Leu Thr Glu Ala Thr Gly Lys Leu Ile Arg Thr Ser 435 440 445 cat att gga aag cct cac cct cag tcc ttt caa cca gca gca gcc aca 1392 His Ile Gly Lys Pro His Pro Gln Ser Phe Gln Pro Ala Ala Ala Thr 450 455 460 caa aaa cta aga cct gct tct cag caa gga gtc cag atg aag aca caa 1440 Gln Lys Leu Arg Pro Ala Ser Gln Gln Gly Val Gln Met Lys Thr Gln 465 470 475 480 ggt ggg gct tca aat cca gct ctc caa ata ggg tcc cat ccc atg tgc 1488 Gly Gly Ala Ser Asn Pro Ala Leu Gln Ile Gly Ser His Pro Met Cys 485 490 495 aag agc tct cag ttc aaa tcc gat cag tcc aac cca tcc aca gtc aaa 1536 Lys Ser Ser Gln Phe Lys Ser Asp Gln Ser Asn Pro Ser Thr Val Lys 500 505 510 cac tcc cag cct aaa ccc ttc cat tct gtg ccc tct caa cct aaa tcc 1584 His Ser Gln Pro Lys Pro Phe His Ser Val Pro Ser Gln Pro Lys Ser 515 520 525 tct cag aca aaa tcc tgt cag tcc cag ccc tcc caa act aaa cct tct 1632 Ser Gln Thr Lys Ser Cys Gln Ser Gln Pro Ser Gln Thr Lys Pro Ser 530 535 540 cca tgc aaa tct act cag cct aag cca agc cag ccc tgg cct ccc cag 1680 Pro Cys Lys Ser Thr Gln Pro Lys Pro Ser Gln Pro Trp Pro Pro Gln 545 550 555 560 tct aag cct tct cag ccc aga ccc cct caa cct aag tca tcc tca acc 1728 Ser Lys Pro Ser Gln Pro Arg Pro Pro Gln Pro Lys Ser Ser Ser Thr 565 570 575 aat cct tca caa gct aag gca cac cac tca aaa gca ggg cag aag agg 1776 Asn Pro Ser Gln Ala Lys Ala His His Ser Lys Ala Gly Gln Lys Arg 580 585 590 gga ggg aag cat taaagagcta actccagaga tctataaagc atatccttta 1828 Gly Gly Lys His 595 cccaggccat tcctatcata tagtaagcag aagagttgcc atgaaagtaa aagactactg 1888 tcattagcat gtaaaacaaa gaaagatata catgaccgaa ttggatatct ttgtttgttt 1948 gtttgagaca gagttcactc ttgtgcccag gctggagtgc aatggcacga tctcggctca 2008 ccgaacctct gcttcctggc ttaaagtgat tctcctgctc agcctctcga gtagctggga 2068 ttacaggcat tgcaccacca cacccagtta ttttgttt 2106 10 7450 DNA Homo sapiens CDS (277)...(6921) 10 cccccctttt ttttttttaa ttcttcagct aaaacagcgg aagaggtgat ttattatatg 60 gttgttacac tcggccacaa ataaacacag aaatagtcca gaatgtcaca ggtccagggc 120 agaggaccaa catgggcatt ttgtttatga gcaaggtggg tctcagaggt gatcggcgat 180 cagagggcga tgaagttcta gatccattga gacaagctct agacagtagc atgcagtccc 240 acaacttgta ccagcatccc cagcgtctgg cattcc atg ttt ctg ctc ctg tgg 294 Met Phe Leu Leu Leu Trp 1 5 cct cca cgg tgc aac aag cta gcg gtt tac ttg gac ctc tgc ctc atc 342 Pro Pro Arg Cys Asn Lys Leu Ala Val Tyr Leu Asp Leu Cys Leu Ile 10 15 20 ttt ctt ctt ttg cgc ttc agc ctg cgc att cgc ttc ttc ctc cac ttg 390 Phe Leu Leu Leu Arg Phe Ser Leu Arg Ile Arg Phe Phe Leu His Leu 25 30 35 gct ctc atg gcg cag agg ttt cca gag agc ctg tca caa aag cat cct 438 Ala Leu Met Ala Gln Arg Phe Pro Glu Ser Leu Ser Gln Lys His Pro 40 45 50 cag cac tct gtg gag tat gag ggt aac att cat aca agt tta gcc att 486 Gln His Ser Val Glu Tyr Glu Gly Asn Ile His Thr Ser Leu Ala Ile 55 60 65 70 gct caa aag cta atg gaa ccg aaa ttg ggg aaa ata aat caa aat tat 534 Ala Gln Lys Leu Met Glu Pro Lys Leu Gly Lys Ile Asn Gln Asn Tyr 75 80 85 gct agc att ata act gaa gct ttc ccg aaa cca aaa gac ata ccc cag 582 Ala Ser Ile Ile Thr Glu Ala Phe Pro Lys Pro Lys Asp Ile Pro Gln 90 95 100 gcc aaa gaa atg ttc att gat aca gtt att tca tct tat aac ata gaa 630 Ala Lys Glu Met Phe Ile Asp Thr Val Ile Ser Ser Tyr Asn Ile Glu 105 110 115 aca gct cat gac agt tca aat tgc agc ata act aga gaa cat ata tgt 678 Thr Ala His Asp Ser Ser Asn Cys Ser Ile Thr Arg Glu His Ile Cys 120 125 130 gtc cat agg aaa aat gaa aat gaa cca gtg tca tta gag acc att cag 726 Val His Arg Lys Asn Glu Asn Glu Pro Val Ser Leu Glu Thr Ile Gln 135 140 145 150 aga gac tat aaa gaa act gct tat gtt gaa gat agg ggt cag gat cac 774 Arg Asp Tyr Lys Glu Thr Ala Tyr Val Glu Asp Arg Gly Gln Asp His 155 160 165 aat ctg ttc tgt aat tca cag tta agc aat gat ata tgg ctg aat gtt 822 Asn Leu Phe Cys Asn Ser Gln Leu Ser Asn Asp Ile Trp Leu Asn Val 170 175 180 aat ttc aaa aaa caa aca gat aga gaa aac caa aat gag gct aaa gag 870 Asn Phe Lys Lys Gln Thr Asp Arg Glu Asn Gln Asn Glu Ala Lys Glu 185 190 195 aat agt gct tca tgt gta gaa aac aac ata gag aac ata tat gga gac 918 Asn Ser Ala Ser Cys Val Glu Asn Asn Ile Glu Asn Ile Tyr Gly Asp 200 205 210 aaa aag cag gat tct cat aca aac gaa aat ttc agc aat ata gat gaa 966 Lys Lys Gln Asp Ser His Thr Asn Glu Asn Phe Ser Asn Ile Asp Glu 215 220 225 230 aag gag gac aaa aat tac cac aat ata gaa att ttg agt tct gaa gaa 1014 Lys Glu Asp Lys Asn Tyr His Asn Ile Glu Ile Leu Ser Ser Glu Glu 235 240 245 ttt tct act aaa ttt aac ttg att tgc aga gaa gat aat gca gtg tca 1062 Phe Ser Thr Lys Phe Asn Leu Ile Cys Arg Glu Asp Asn Ala Val Ser 250 255 260 gca gca act gca tta tta gag agt gaa gaa gat acc att agt gcc gtg 1110 Ala Ala Thr Ala Leu Leu Glu Ser Glu Glu Asp Thr Ile Ser Ala Val 265 270 275 aaa caa aaa gat act gaa aat act gga aga agt gta gag cat ttg gct 1158 Lys Gln Lys Asp Thr Glu Asn Thr Gly Arg Ser Val Glu His Leu Ala 280 285 290 tcc acg aca ttt ccc aaa act gca agt tct tca gtg tgt gta gcc tca 1206 Ser Thr Thr Phe Pro Lys Thr Ala Ser Ser Ser Val Cys Val Ala Ser 295 300 305 310 aat gct gca ata cag ata gct agt gct act atg cct gca tta agc cta 1254 Asn Ala Ala Ile Gln Ile Ala Ser Ala Thr Met Pro Ala Leu Ser Leu 315 320 325 aat aat gac gat cac cag ata tac cag ttt aaa gaa act tgt tct tct 1302 Asn Asn Asp Asp His Gln Ile Tyr Gln Phe Lys Glu Thr Cys Ser Ser 330 335 340 gaa agt cca gat ttt ggt ttg tta gta aaa cat agg gtt tct gat tgt 1350 Glu Ser Pro Asp Phe Gly Leu Leu Val Lys His Arg Val Ser Asp Cys 345 350 355 gaa att gat acg gat aaa aat aaa tca caa gaa tca ttt cat caa tca 1398 Glu Ile Asp Thr Asp Lys Asn Lys Ser Gln Glu Ser Phe His Gln Ser 360 365 370 ata aat gag aac tta gtt ctt cag agc att gaa ttg gaa agt gaa att 1446 Ile Asn Glu Asn Leu Val Leu Gln Ser Ile Glu Leu Glu Ser Glu Ile 375 380 385 390 gaa ata gaa tta gaa gat tgt gat gat gct ttt ata ttt caa caa gat 1494 Glu Ile Glu Leu Glu Asp Cys Asp Asp Ala Phe Ile Phe Gln Gln Asp 395 400 405 aca cat agc cat gaa aac atg ctt tgt gaa gaa ttt gtg acc tca tat 1542 Thr His Ser His Glu Asn Met Leu Cys Glu Glu Phe Val Thr Ser Tyr 410 415 420 aag gct ctg aag tct cgt atc agt tgg gaa ggt ctg tta gca ctt gat 1590 Lys Ala Leu Lys Ser Arg Ile Ser Trp Glu Gly Leu Leu Ala Leu Asp 425 430 435 aac ggg gag atg gaa gtt ttg gaa agc acc aca gga agg gag aat agt 1638 Asn Gly Glu Met Glu Val Leu Glu Ser Thr Thr Gly Arg Glu Asn Ser 440 445 450 gat cag cat tat tct aag gaa agt aac tat ttt tat tcc tct aca caa 1686 Asp Gln His Tyr Ser Lys Glu Ser Asn Tyr Phe Tyr Ser Ser Thr Gln 455 460 465 470 aac aat gaa aca gaa ctt acc agc cca att tta ctt cca gat cta caa 1734 Asn Asn Glu Thr Glu Leu Thr Ser Pro Ile Leu Leu Pro Asp Leu Gln 475 480 485 att aaa att act aat ata ttt agg cca gga ttc agc ccg aca gct gac 1782 Ile Lys Ile Thr Asn Ile Phe Arg Pro Gly Phe Ser Pro Thr Ala Asp 490 495 500 tcc ctt gca ttg aaa gat agt ttt tgc aca cat gta act gaa gcc aca 1830 Ser Leu Ala Leu Lys Asp Ser Phe Cys Thr His Val Thr Glu Ala Thr 505 510 515 aaa ccg gaa ata aat aag gaa gat gga gaa att cta gga ttt gac att 1878 Lys Pro Glu Ile Asn Lys Glu Asp Gly Glu Ile Leu Gly Phe Asp Ile 520 525 530 tat tcc cag cct ttt ggt gaa aat gca gat tat cca tgt gaa gat aaa 1926 Tyr Ser Gln Pro Phe Gly Glu Asn Ala Asp Tyr Pro Cys Glu Asp Lys 535 540 545 550 gtt gat aat ata agg caa gaa tca ggg cca gtg agt aac tct gaa atc 1974 Val Asp Asn Ile Arg Gln Glu Ser Gly Pro Val Ser Asn Ser Glu Ile 555 560 565 tcc ctt tct ttt gac ttg agt cgt aat aca gat gtg aat cat acg tct 2022 Ser Leu Ser Phe Asp Leu Ser Arg Asn Thr Asp Val Asn His Thr Ser 570 575 580 gaa aat cag aac agt gaa tct ttg ttt act gaa cct tct aat gtc aca 2070 Glu Asn Gln Asn Ser Glu Ser Leu Phe Thr Glu Pro Ser Asn Val Thr 585 590 595 aca ata gat gat gga agc aga tgt ttc ttt aca aaa tca aaa act gac 2118 Thr Ile Asp Asp Gly Ser Arg Cys Phe Phe Thr Lys Ser Lys Thr Asp 600 605 610 tat aat gat acc aaa aat aaa aag gag gta gaa tca aga att agc aaa 2166 Tyr Asn Asp Thr Lys Asn Lys Lys Glu Val Glu Ser Arg Ile Ser Lys 615 620 625 630 agg aag cta cat ata tct tcc agg gat cag aac ata cca cat aaa gat 2214 Arg Lys Leu His Ile Ser Ser Arg Asp Gln Asn Ile Pro His Lys Asp 635 640 645 tta aga cga cat aaa att tat ggg aga aag agg agg cta acc agt caa 2262 Leu Arg Arg His Lys Ile Tyr Gly Arg Lys Arg Arg Leu Thr Ser Gln 650 655 660 gac tca tct gag tgt ttc tct tca tta tcc caa gga cga att aaa aca 2310 Asp Ser Ser Glu Cys Phe Ser Ser Leu Ser Gln Gly Arg Ile Lys Thr 665 670 675 ttt tca cag tca gaa aag cac att aag agt gtc cta aat atc cta agt 2358 Phe Ser Gln Ser Glu Lys His Ile Lys Ser Val Leu Asn Ile Leu Ser 680 685 690 gat gaa gca tct tta tgt aaa agc aaa tgt ctt tcc aga aaa cta gac 2406 Asp Glu Ala Ser Leu Cys Lys Ser Lys Cys Leu Ser Arg Lys Leu Asp 695 700 705 710 aaa gca gtt gtt cac tta aaa aaa gct cat aga aga gtt cac aca tct 2454 Lys Ala Val Val His Leu Lys Lys Ala His Arg Arg Val His Thr Ser 715 720 725 ttg cag ctt ata act aaa gta gga gaa gaa aga aag ggc cca tta cca 2502 Leu Gln Leu Ile Thr Lys Val Gly Glu Glu Arg Lys Gly Pro Leu Pro 730 735 740 aaa tca tat gca ata ata tgc aat aat ttc tgg gaa agt tgt gac ctt 2550 Lys Ser Tyr Ala Ile Ile Cys Asn Asn Phe Trp Glu Ser Cys Asp Leu 745 750 755 caa ggt tat agt tct gtg tct caa aga aaa tat tat tct act aag cat 2598 Gln Gly Tyr Ser Ser Val Ser Gln Arg Lys Tyr Tyr Ser Thr Lys His 760 765 770 ttt tcg tca aaa aga aaa tat gac aaa cgg aga aag aaa aga gct cca 2646 Phe Ser Ser Lys Arg Lys Tyr Asp Lys Arg Arg Lys Lys Arg Ala Pro 775 780 785 790 aaa gct gat att tct aaa tca tta acc cat gtg tca aag cac aag tct 2694 Lys Ala Asp Ile Ser Lys Ser Leu Thr His Val Ser Lys His Lys Ser 795 800 805 tat aaa aca agt gga gag aaa aaa tgc ctt tct agg aaa agt atg gct 2742 Tyr Lys Thr Ser Gly Glu Lys Lys Cys Leu Ser Arg Lys Ser Met Ala 810 815 820 agc agt gtc tca aaa agt cac ccc acc acc agt cac atg gga gaa ttt 2790 Ser Ser Val Ser Lys Ser His Pro Thr Thr Ser His Met Gly Glu Phe 825 830 835 tgt aat caa gaa cat cct gaa tca cag ttg cct gta tcc tcc aca tcc 2838 Cys Asn Gln Glu His Pro Glu Ser Gln Leu Pro Val Ser Ser Thr Ser 840 845 850 caa agt aca agt cag tca gtt tat tat aat agc agt gta agc aat cca 2886 Gln Ser Thr Ser Gln Ser Val Tyr Tyr Asn Ser Ser Val Ser Asn Pro 855 860 865 870 agt tta tca gaa gaa cat cag ccc ttt tct gga aaa act gca tat ctg 2934 Ser Leu Ser Glu Glu His Gln Pro Phe Ser Gly Lys Thr Ala Tyr Leu 875 880 885 ttt tcc cca gac cac tca gat gag aaa cta ata gaa aaa gaa aat caa 2982 Phe Ser Pro Asp His Ser Asp Glu Lys Leu Ile Glu Lys Glu Asn Gln 890 895 900 att gat aca gca ttt tta tct agc act agt aaa tat gaa aag ctt gaa 3030 Ile Asp Thr Ala Phe Leu Ser Ser Thr Ser Lys Tyr Glu Lys Leu Glu 905 910 915 aaa cat tca gca aat cat aat gtt aaa gat gca act aaa gaa aac agt 3078 Lys His Ser Ala Asn His Asn Val Lys Asp Ala Thr Lys Glu Asn Ser 920 925 930 tgt gac gct aat gaa gta ata aat gaa agt aat tct gta tct tta agt 3126 Cys Asp Ala Asn Glu Val Ile Asn Glu Ser Asn Ser Val Ser Leu Ser 935 940 945 950 tgc ata aaa gaa aac ata aat tct agt aca ggc aac gat tgt gat gca 3174 Cys Ile Lys Glu Asn Ile Asn Ser Ser Thr Gly Asn Asp Cys Asp Ala 955 960 965 act tgc ata ggt cac aca aag gcg aaa act gac gta ctt ata tca gtc 3222 Thr Cys Ile Gly His Thr Lys Ala Lys Thr Asp Val Leu Ile Ser Val 970 975 980 tta gat tca aat gtg aag cac ttt tta aat gat ctc tac caa caa ggt 3270 Leu Asp Ser Asn Val Lys His Phe Leu Asn Asp Leu Tyr Gln Gln Gly 985 990 995 aac ctt att tta tct gat tgt aaa aga aac ctg gaa gta aag tgg aca 3318 Asn Leu Ile Leu Ser Asp Cys Lys Arg Asn Leu Glu Val Lys Trp Thr 1000 1005 1010 gat cct att gag aga ccc ata caa aac att att aca gga aac ttc ctt 3366 Asp Pro Ile Glu Arg Pro Ile Gln Asn Ile Ile Thr Gly Asn Phe Leu 1015 1020 1025 1030 atg ggc cca tta aac cta act ttg ata gca agt aaa aag tac agt att 3414 Met Gly Pro Leu Asn Leu Thr Leu Ile Ala Ser Lys Lys Tyr Ser Ile 1035 1040 1045 cct cag tta tca gcc gct gca gtg aca gat agt gag gga gaa tct tca 3462 Pro Gln Leu Ser Ala Ala Ala Val Thr Asp Ser Glu Gly Glu Ser Ser 1050 1055 1060 aaa tct tac ttg gat aag cag aga att ctt act gta gat tct ttt gca 3510 Lys Ser Tyr Leu Asp Lys Gln Arg Ile Leu Thr Val Asp Ser Phe Ala 1065 1070 1075 gca tcc agt act gta cca cac tgt gag cag agc tgt aga gaa aaa gag 3558 Ala Ser Ser Thr Val Pro His Cys Glu Gln Ser Cys Arg Glu Lys Glu 1080 1085 1090 ctt cta aag aca gaa cag tgc tct tca ggt aat tgc ctc cat aca gat 3606 Leu Leu Lys Thr Glu Gln Cys Ser Ser Gly Asn Cys Leu His Thr Asp 1095 1100 1105 1110 ggg aat gaa aca aat gtc act gag aat tat gag ttg gat gta gca tca 3654 Gly Asn Glu Thr Asn Val Thr Glu Asn Tyr Glu Leu Asp Val Ala Ser 1115 1120 1125 gga act gaa gaa gat aaa agt tat ggg gaa aat ata gtg gaa tta tct 3702 Gly Thr Glu Glu Asp Lys Ser Tyr Gly Glu Asn Ile Val Glu Leu Ser 1130 1135 1140 tcc agt gat agt tct ctg ctt tta aaa gat aat gta aaa ggc tcc tct 3750 Ser Ser Asp Ser Ser Leu Leu Leu Lys Asp Asn Val Lys Gly Ser Ser 1145 1150 1155 tca gaa aca tgt att gtg aag aaa gac act gag gac aga ata acg tgg 3798 Ser Glu Thr Cys Ile Val Lys Lys Asp Thr Glu Asp Arg Ile Thr Trp 1160 1165 1170 aaa gtt aaa caa gcg gaa aaa gca aaa gat tct gtt tac aaa aga agc 3846 Lys Val Lys Gln Ala Glu Lys Ala Lys Asp Ser Val Tyr Lys Arg Ser 1175 1180 1185 1190 atg act gaa gga tca act gtt aat act gag tac aaa aat caa aag aat 3894 Met Thr Glu Gly Ser Thr Val Asn Thr Glu Tyr Lys Asn Gln Lys Asn 1195 1200 1205 cag atc tca gaa gaa tcc tgc tta aat gag aaa att att aca act aac 3942 Gln Ile Ser Glu Glu Ser Cys Leu Asn Glu Lys Ile Ile Thr Thr Asn 1210 1215 1220 ttg att gat tcc cat ctg agc act aaa aat act acc act gag tca gtc 3990 Leu Ile Asp Ser His Leu Ser Thr Lys Asn Thr Thr Thr Glu Ser Val 1225 1230 1235 cct ttg aag aac aca gtt tct aat ccg ctt aac aaa aga gag aag aac 4038 Pro Leu Lys Asn Thr Val Ser Asn Pro Leu Asn Lys Arg Glu Lys Asn 1240 1245 1250 ccc caa att aaa gtt agt aaa gac tcg cag tct gac ttg aca tta cat 4086 Pro Gln Ile Lys Val Ser Lys Asp Ser Gln Ser Asp Leu Thr Leu His 1255 1260 1265 1270 tca gaa ata gcc tat att tcc aaa cca gga att cta gga gtt aat cat 4134 Ser Glu Ile Ala Tyr Ile Ser Lys Pro Gly Ile Leu Gly Val Asn His 1275 1280 1285 acg cct att tta cct gcc cac tct gaa acc tgt aaa gtc cct act ctt 4182 Thr Pro Ile Leu Pro Ala His Ser Glu Thr Cys Lys Val Pro Thr Leu 1290 1295 1300 ctg aag aaa cct gcg tca tac gtg agt gat ttt aaa gaa aaa cat tgc 4230 Leu Lys Lys Pro Ala Ser Tyr Val Ser Asp Phe Lys Glu Lys His Cys 1305 1310 1315 tca gct aat cat acg gcc ctt ata gct aat cta tct caa att ttg cag 4278 Ser Ala Asn His Thr Ala Leu Ile Ala Asn Leu Ser Gln Ile Leu Gln 1320 1325 1330 agg gca gat gaa gca tca tct ttg cag att cta cag gaa gaa act aag 4326 Arg Ala Asp Glu Ala Ser Ser Leu Gln Ile Leu Gln Glu Glu Thr Lys 1335 1340 1345 1350 gtt tgt cta aat att ctc cct tta ttt gtg gaa gct ttt gaa aga aag 4374 Val Cys Leu Asn Ile Leu Pro Leu Phe Val Glu Ala Phe Glu Arg Lys 1355 1360 1365 caa gaa tgt tca gtt gaa caa atc ctg att tca aga gaa ctg ttg gta 4422 Gln Glu Cys Ser Val Glu Gln Ile Leu Ile Ser Arg Glu Leu Leu Val 1370 1375 1380 gac caa aac ctg tgg aat aat tgc aaa cac aca tta aaa cca tgt gct 4470 Asp Gln Asn Leu Trp Asn Asn Cys Lys His Thr Leu Lys Pro Cys Ala 1385 1390 1395 gtt gac act ttg gta gaa ctt caa atg atg atg gaa aca att caa ttc 4518 Val Asp Thr Leu Val Glu Leu Gln Met Met Met Glu Thr Ile Gln Phe 1400 1405 1410 att gaa aac aaa aaa agg cac tta gaa ggt gaa cca aca ttg cga agc 4566 Ile Glu Asn Lys Lys Arg His Leu Glu Gly Glu Pro Thr Leu Arg Ser 1415 1420 1425 1430 ttg ctt tgg tat gat gaa aca ctg tat gct gag ctt ctt gga aaa cca 4614 Leu Leu Trp Tyr Asp Glu Thr Leu Tyr Ala Glu Leu Leu Gly Lys Pro 1435 1440 1445 cgt gga ttt caa cag cag tct aat ttc tat cct ggt ttc caa gga aga 4662 Arg Gly Phe Gln Gln Gln Ser Asn Phe Tyr Pro Gly Phe Gln Gly Arg 1450 1455 1460 tta aaa tat aat gca ttc tgt gag tta cag act tac cat gat caa tta 4710 Leu Lys Tyr Asn Ala Phe Cys Glu Leu Gln Thr Tyr His Asp Gln Leu 1465 1470 1475 gtt gaa ttg ctt gag gaa aca aaa agg gaa aag aat tca tac tat gta 4758 Val Glu Leu Leu Glu Glu Thr Lys Arg Glu Lys Asn Ser Tyr Tyr Val 1480 1485 1490 ttc tta aag tac aaa cga cag gtt aat gaa tgt gaa gcc ata atg gag 4806 Phe Leu Lys Tyr Lys Arg Gln Val Asn Glu Cys Glu Ala Ile Met Glu 1495 1500 1505 1510 cat tgt tcc gat tgc ttt gat ttt tct ctt tct gtt cca ttt acc tgt 4854 His Cys Ser Asp Cys Phe Asp Phe Ser Leu Ser Val Pro Phe Thr Cys 1515 1520 1525 gga gtt aac ttt gga gat agt tta gaa gac ctg gaa atc tta aga aaa 4902 Gly Val Asn Phe Gly Asp Ser Leu Glu Asp Leu Glu Ile Leu Arg Lys 1530 1535 1540 agt act tta aag ttg atc aat gta tgt ggg gac tct cct aaa gtt cat 4950 Ser Thr Leu Lys Leu Ile Asn Val Cys Gly Asp Ser Pro Lys Val His 1545 1550 1555 tcg tat cca gga aaa cag gac cat ctg tgg att atc ata gaa atg atc 4998 Ser Tyr Pro Gly Lys Gln Asp His Leu Trp Ile Ile Ile Glu Met Ile 1560 1565 1570 tcc tca aag gtt aat ttt att aag aac aac gag gca gta cgt gtt aaa 5046 Ser Ser Lys Val Asn Phe Ile Lys Asn Asn Glu Ala Val Arg Val Lys 1575 1580 1585 1590 ata tct ctt tat ggt ctg gaa cat atc ttt ttt gat gct gca aaa aat 5094 Ile Ser Leu Tyr Gly Leu Glu His Ile Phe Phe Asp Ala Ala Lys Asn 1595 1600 1605 ctt gtt tgg aaa gag aga aca caa tcc ttc agc aaa aaa tac tca caa 5142 Leu Val Trp Lys Glu Arg Thr Gln Ser Phe Ser Lys Lys Tyr Ser Gln 1610 1615 1620 aag aag gac gaa gaa agg cta ctc aga gtg aat aaa tgt gcc ttt tct 5190 Lys Lys Asp Glu Glu Arg Leu Leu Arg Val Asn Lys Cys Ala Phe Ser 1625 1630 1635 aag ttg cag aag ata tat gat act ttg tct aaa gat tta aac aat gaa 5238 Lys Leu Gln Lys Ile Tyr Asp Thr Leu Ser Lys Asp Leu Asn Asn Glu 1640 1645 1650 cca att tcc cct att ggg ctt gag gag gat act ata att gct tcc aga 5286 Pro Ile Ser Pro Ile Gly Leu Glu Glu Asp Thr Ile Ile Ala Ser Arg 1655 1660 1665 1670 aag tca gat cat cca ata acg aag cac att agc ata gaa aat tct aaa 5334 Lys Ser Asp His Pro Ile Thr Lys His Ile Ser Ile Glu Asn Ser Lys 1675 1680 1685 ttt aac agt aat ttg ctt gca cac cca gat att tgt tgt att agt gag 5382 Phe Asn Ser Asn Leu Leu Ala His Pro Asp Ile Cys Cys Ile Ser Glu 1690 1695 1700 ata ttg gat cag gct gaa ttt gca gac ctt aaa aaa tta cag gat ctc 5430 Ile Leu Asp Gln Ala Glu Phe Ala Asp Leu Lys Lys Leu Gln Asp Leu 1705 1710 1715 acc ttg aga tgt aca gat cac tta gaa att tta aaa aaa tac ttt cag 5478 Thr Leu Arg Cys Thr Asp His Leu Glu Ile Leu Lys Lys Tyr Phe Gln 1720 1725 1730 atg cta caa gat aat aac atg gat aat att ttt atc aca gaa gaa aat 5526 Met Leu Gln Asp Asn Asn Met Asp Asn Ile Phe Ile Thr Glu Glu Asn 1735 1740 1745 1750 gtt tta gac gtg gtg ata aac cac agc cat gag gct atc att tta aag 5574 Val Leu Asp Val Val Ile Asn His Ser His Glu Ala Ile Ile Leu Lys 1755 1760 1765 cct gaa gct att gaa atg tat att gaa atc gtc atg gtc tca gaa aca 5622 Pro Glu Ala Ile Glu Met Tyr Ile Glu Ile Val Met Val Ser Glu Thr 1770 1775 1780 att cac ttt ctt aaa aac tca ata gca aag aaa cta gac aaa cag agg 5670 Ile His Phe Leu Lys Asn Ser Ile Ala Lys Lys Leu Asp Lys Gln Arg 1785 1790 1795 ttt cga ggt atg ctt tgg ttt gat ttg tca ctt ctt cct gag ctg gtt 5718 Phe Arg Gly Met Leu Trp Phe Asp Leu Ser Leu Leu Pro Glu Leu Val 1800 1805 1810 cag tgc caa gaa aaa atg gct tct ttt tca ttt ctt aaa gat aac tca 5766 Gln Cys Gln Glu Lys Met Ala Ser Phe Ser Phe Leu Lys Asp Asn Ser 1815 1820 1825 1830 aca gat gtt tgc ctt tgg aaa gtg ata gag act gct gtt tcc gaa ctt 5814 Thr Asp Val Cys Leu Trp Lys Val Ile Glu Thr Ala Val Ser Glu Leu 1835 1840 1845 aag aaa gat ctg gat att atc tgg caa aat ata atg aaa gct gtt aaa 5862 Lys Lys Asp Leu Asp Ile Ile Trp Gln Asn Ile Met Lys Ala Val Lys 1850 1855 1860 ttt gct cat atg cta ttc att tgc ttc ttc aag gag aac ttc aag gaa 5910 Phe Ala His Met Leu Phe Ile Cys Phe Phe Lys Glu Asn Phe Lys Glu 1865 1870 1875 cct ttc aga aat aaa aaa gct tct gaa gaa gtc caa gta tta att cca 5958 Pro Phe Arg Asn Lys Lys Ala Ser Glu Glu Val Gln Val Leu Ile Pro 1880 1885 1890 cat ata ttg acc ttt gtg cca tat ata gca tcc ata aat tat gga agc 6006 His Ile Leu Thr Phe Val Pro Tyr Ile Ala Ser Ile Asn Tyr Gly Ser 1895 1900 1905 1910 act gtg aca gag tta gaa tac aac tac aat caa ttt tct aca ctg ctg 6054 Thr Val Thr Glu Leu Glu Tyr Asn Tyr Asn Gln Phe Ser Thr Leu Leu 1915 1920 1925 aag aat gta atg tct gcc cct agg aaa gat tta gga aaa atg gcc cac 6102 Lys Asn Val Met Ser Ala Pro Arg Lys Asp Leu Gly Lys Met Ala His 1930 1935 1940 att agg aaa gtc atg aaa acg att gaa cat atg aag atg ata tgt act 6150 Ile Arg Lys Val Met Lys Thr Ile Glu His Met Lys Met Ile Cys Thr 1945 1950 1955 aaa aat gct gaa cta acc att tcc ttt ttc cta tgc caa atg ctg tat 6198 Lys Asn Ala Glu Leu Thr Ile Ser Phe Phe Leu Cys Gln Met Leu Tyr 1960 1965 1970 aac aga agg aag att tta cag ctg aag aga aaa gaa aaa atg aat att 6246 Asn Arg Arg Lys Ile Leu Gln Leu Lys Arg Lys Glu Lys Met Asn Ile 1975 1980 1985 1990 cat att gta aaa cct ggg gaa aat aac aat aaa ttt agt att tct acg 6294 His Ile Val Lys Pro Gly Glu Asn Asn Asn Lys Phe Ser Ile Ser Thr 1995 2000 2005 atg ttg ccc cca gta tca gag tgc ata aac aaa aac atc tca aat tcc 6342 Met Leu Pro Pro Val Ser Glu Cys Ile Asn Lys Asn Ile Ser Asn Ser 2010 2015 2020 tct aaa aaa cga ccg agc act gta gac aaa tgt gaa gac tct cag gaa 6390 Ser Lys Lys Arg Pro Ser Thr Val Asp Lys Cys Glu Asp Ser Gln Glu 2025 2030 2035 cag cag caa gat act act gtt tcc agt tgt aaa aag cta aag gta gac 6438 Gln Gln Gln Asp Thr Thr Val Ser Ser Cys Lys Lys Leu Lys Val Asp 2040 2045 2050 atg aaa gat gtc aca aaa atc aac aga gaa aag gca aca ttc aag cat 6486 Met Lys Asp Val Thr Lys Ile Asn Arg Glu Lys Ala Thr Phe Lys His 2055 2060 2065 2070 cca agg act aca gga tct cat ccc aaa agc gaa aac aaa ata gta cca 6534 Pro Arg Thr Thr Gly Ser His Pro Lys Ser Glu Asn Lys Ile Val Pro 2075 2080 2085 agt tca tgt gac agt ctg aaa aga aat cat tta acg cca aaa aag gtt 6582 Ser Ser Cys Asp Ser Leu Lys Arg Asn His Leu Thr Pro Lys Lys Val 2090 2095 2100 gaa atg caa aga tca cta cct ggc tca ctt tta ccc tta gag aac cca 6630 Glu Met Gln Arg Ser Leu Pro Gly Ser Leu Leu Pro Leu Glu Asn Pro 2105 2110 2115 aaa gac act tgc gca tca aag tcg gaa agc aaa ata gac tta act gtt 6678 Lys Asp Thr Cys Ala Ser Lys Ser Glu Ser Lys Ile Asp Leu Thr Val 2120 2125 2130 tca tct gat cac ttc agt gga caa cag gaa aat tta aat agc atg aag 6726 Ser Ser Asp His Phe Ser Gly Gln Gln Glu Asn Leu Asn Ser Met Lys 2135 2140 2145 2150 aaa aga aat gtg aac ttc agt gct gct gaa aca aaa agt gat aag aaa 6774 Lys Arg Asn Val Asn Phe Ser Ala Ala Glu Thr Lys Ser Asp Lys Lys 2155 2160 2165 gat tgt gct gct ttt gca att tgt gac caa aaa agt gta cat ggc aca 6822 Asp Cys Ala Ala Phe Ala Ile Cys Asp Gln Lys Ser Val His Gly Thr 2170 2175 2180 ttt tca cca gac cat ggg aca ctt ttg cag aaa ttt ctt aaa aat tcc 6870 Phe Ser Pro Asp His Gly Thr Leu Leu Gln Lys Phe Leu Lys Asn Ser 2185 2190 2195 cac agg gtt gtt tat aat agc aat ata cat aca cat ttg gct agt act 6918 His Arg Val Val Tyr Asn Ser Asn Ile His Thr His Leu Ala Ser Thr 2200 2205 2210 agg tgaataggaa aataaatcat gctgtatgta tacaataaga ggtcaagttg 6971 Arg 2215 ccaataaatt attactgtta atgttctggg aaatgctgaa actatgctaa gtgggggaga 7031 gggaaagcag gtattgcagt tttgtagtga agatgggctt tggagtcata tctgagatgt 7091 aagtagcagc ttttaaattc tagctatgac cctgtgcaga tcacttaact tttgagtgtc 7151 aggatgtttg gaaggacaag acaggaaagt gttttaatac agggttcagt atttagtaag 7211 ccttcaataa gtgatattac atacatgtaa taaaaactaa gcattgaaag gactaggaaa 7271 aatgcatcaa atgttagttc tgcaggttat agaattatac ttttatgtaa ttttaaaatt 7331 tcagttatga acatgtttgt ccattacaaa cttataatag ctgaaaaaca gggttgtgag 7391 aacagcttca gttaaaattg tcctgtctag ttttgaatat tcaagaacag aaagccttt 7450 

1. A polynucleotide comprising a base sequence that is identical or substantially identical with a base sequence represented by SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID No: 8, SEQ ID NO: 9, and SEQ ID NO:
 10. 2. A recombinant vector containing the polynucleotide according to claim
 1. 3. A transformant containing the recombinant vector according to claim
 2. 4. The polynucleotide according to claim 1 labeled with radioisotope, enzyme, or fluorochrome.
 5. A polypeptide comprising an amino acid sequence that is identical or substantially identical with an amino acid sequence encoded by the polynucleotide according to claim
 1. 6. An antibody against the polypeptide according to claim
 5. 7. A hybridoma producing the antibody according to claim
 6. 8. A diagnostic product for autoimmune diseases containing the polypeptide according to claim
 5. 9. A diagnostic kit of autoimmune diseases for screening serum of a GVHD or a GVL patient, wherein the diagnostic kit contains the polypeptide according to claim
 5. 10. A kit for examining diseases for analyzing living tissues of an AML, a CML, a GVHD, or a GVL patient, wherein the kit contains the antibody according to claim
 6. 11. A remedy for cancer for treating a cancer by strengthening the defense mechanism of a living body against cancer cells, wherein the remedy contains the polynucleotide according to claim
 1. 12. A remedy for cancer for treating a cancer by strengthening the defense mechanism of a living body against cancer cells, wherein the remedy contains the polypeptide according to claim
 5. 13. A remedy for cancer for treating a cancer by strengthening the defense mechanism of a living body against cancer cells, wherein the remedy contains the polynucleotide according to claim 1 and the polypeptide including an amino acid sequence that is identical or substantially identical with an amino acid sequence encoded by said polynucleotide.
 14. The remedy for cancer according to any one of claims 11 to 13, wherein the remedy is prepared as an injection.
 15. A vaccine for preventing development of a cancer by allowing a living body to acquire the defense mechanism of the living body against cancer cells, wherein the vaccine contains the polynucleotide according to claim
 1. 16. A vaccine for preventing development of a cancer by allowing a living body to acquire the defense mechanism of the living body against cancer cells, wherein the vaccine contains the polypeptide according to claim
 5. 17. A vaccine for preventing development of a cancer by allowing a living body to acquire the defense mechanism of the living body against cancer cells, wherein the vaccine contains the polynucleotide according to claim 1 and the polypeptide including an amino acid sequence that is identical or substantially identical with an amino acid sequence encoded by said polynucleotide.
 18. The vaccine according to any one of claims 15 to 17, wherein the vaccine is prepared as an injection.
 19. A DNA chip containing the polynucleotide according to claim
 1. 